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The colonization of medical devices such as catheters, topical wound dressings, and surgical implants by micro‐organisms is an ongoing problem, particularly as many strains of bacteria are becoming resistant to antibiotics. Such a problem may be addressed by a material surface that is able to provide a slow release of a disinfectant during its period of usage. To achieve this objective, a novel material was prepared in which a quaternary ammonium salt was covalently bound onto a polyethylene backbone via a hydrolyzable ester linkage, which provided a slow release of the disinfecting agent. A low‐density polyethylene film was treated with glow discharge followed by the graft polymerization of acrylic acid. A tertiary amine function was introduced onto the film by the esterification of the carboxylic acid groups, via an acid chloride intermediate, with 4‐hydroxy‐N‐methyl piperidine. The tertiary amine on the piperidine was then quaternized with a series of alkyl bromides of various chain lengths. The quaternary ammonium salt was released slowly by the hydrolysis of the ester bond over a 4‐h period. To test the efficacy of the quaternary ammonium function itself, soluble compounds were prepared as follows. 4‐Hydroxy‐N‐methyl piperidine was esterified with acetic anhydride and a corresponding series of quaternary ammonium salts prepared again by a reaction with alkyl bromides of various chain lengths. A preliminary microbiological survey of the materials included an investigation of the effect of the chain length as well as the efficacy of the soluble quaternary salts themselves. As expected, only the longer alkyl chains provided quaternary ammonium salts with bactericidal properties, chain lengths of less than 10 carbon atoms proving ineffective. Both the polymer‐bound and soluble long‐chain quaternary ammonium salts were effective against suspensions of Staphylococcus aureus and Escherichia coli. The results therefore indicate that such a system may well be useful in the development of biomedical materials such as surgical implants or dressings in which a slow release of a disinfectant or other physiologically active agent such as an anti‐inflammatory drug may be required. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 538–545, 2006

The colonization of medical devices by micro‐organisms is an ongoing problem, particularly as many strains of bacteria are becoming resistant to antibiotics. One method by which this could be addressed is the production of a surface that will kill bacteria on contact without releasing the disinfecting agent into solution. Self‐disinfecting surfaces were prepared in which a quaternary ammonium salt was covalently bound onto a polyethylene film by a stable linkage. To achieve this, a low‐density polyethylene film was treated with glow discharge followed by the graft polymerization of acrylic acid. The acid chloride derivative was then prepared. α,ω‐Dibromoalkanes of various chain lengths were reacted with potassium phthalimide to form an N‐alkylphthalimido group, and this was followed by an excess of piperidine to produce a tertiary amino group at the opposite end of the alkyl chain. The hydrolysis of the phthalimido group produced a primary amino function that was coupled to the grafted poly(acryl chloride). A reaction with octadecyl bromide resulted in the production of a quaternary ammonium salt. The amide linkage by which the quaternary ammonium salt was attached to the polymer was stable, and no release of the disinfecting moiety took place in solution. Soluble compounds containing a similar quaternary ammonium function were prepared through the reaction of the primary amine group with acetyl chloride rather than the polymeric acid chloride to form substituted N‐acetamides. In a microbiological pilot study, both the polymer‐bound and soluble quaternary ammonium salts were effective against suspensions of Staphylococcus aureus, Escherichia coli, and Saccharomyces cerevisiae. The results show that a self‐disinfecting surface can be produced in which the quaternary ammonium function is an effective bacteriocide that remains bound to the polymer surface. In addition, the materials were toxic to a mammalian cell line (Chinese hamster ovary cells). © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 381–389, 2006

A range of chemically modified energetic polymers has been synthesized. The structural modification involves the incorporation of a double bond into the polymeric binder which allows subsequent degradation of the material by ozonolysis thus providing an environmentally safe method for the disposal of munitions. This was achieved by reacting the energetic prepolymer, poly-NIMMO, with a range of unsaturated diisocyanates where the double bond was incorporated into the cross-linking i.e. “curing” agent. Firstly, poly-NIMMO and cis-1,4-but-2-ene diol were reacted with hexamethylene diisocyanate. Secondly, three unsaturated diisocyanates (two novel) were prepared in situ from their corresponding diacyl azides and reacted with poly-NIMMO. The three diisocyanates prepared were 1,4-diphenoxy-trans-2-butene-diisocyanate, phenylene diacrylic di-isocyanate, and trans-2-butene-1,4-diisocyanate. The latter has been reported previously^(1,2) although never isolated and characterized; however, this has been achieved successfully in this study. GPC of the chain extended polymers prepared by both methods showed the expected increase in molecular weight distribution. A corresponding decrease following ozonolysis occurred particularly with the polymers prepared from 1,4-diphenoxy-trans-2-butene-diisocyanate and phenylene diacrylic diisocyanate.

A range of chemically modified energetic polymers has been synthesized. The structural modification involves the incorporation of a double bond into the polymeric binder which allows subsequent degradation of the material by ozonolysis thus providing an environmentally safe method for the disposal of munitions. This was achieved by reacting the energetic prepolymer, poly-NIMMO, with a range of unsaturated diisocyanates where the double bond was incorporated into the cross-linking i.e. “curing” agent. Firstly, poly-NIMMO and cis-1,4-but-2-ene diol were reacted with hexamethylene diisocyanate. Secondly, three unsaturated diisocyanates (two novel) were prepared in situ from their corresponding diacyl azides and reacted with poly-NIMMO. The three diisocyanates prepared were 1,4-diphenoxy-trans-2-butene-diisocyanate, phenylene diacrylic di-isocyanate, and trans-2-butene-1,4-diisocyanate. The latter has been reported previously^(1,2) although never isolated and characterized; however, this has been achieved successfully in this study. GPC of the chain extended polymers prepared by both methods showed the expected increase in molecular weight distribution. A corresponding decrease following ozonolysis occurred particularly with the polymers prepared from 1,4-diphenoxy-trans-2-butene-diisocyanate and phenylene diacrylic diisocyanate.

A range of chemically modified energetic polymers has been synthesized. The structural modification involves the incorporation of a double bond into the polymeric binder which allows subsequent degradation of the material by ozonolysis thus providing an environmentally safe method for the disposal of munitions. This was achieved by reacting the energetic prepolymer, poly‐NIMMO, with a range of unsaturated diisocyanates where the double bond was incorporated into the cross‐linking i.e.“curing” agent. Firstly, poly‐NIMMO and cis‐1,4‐but‐2‐ene diol were reacted with hexamethylene diisocyanate. Secondly, three unsaturated diisocyanates (two novel) were prepared in situfrom their corresponding diacyl azides and reacted with poly‐NIMMO. The three diisocyanates prepared were 1,4‐diphenoxy‐trans‐2‐butene‐diisocyanate, phenylene diacrylic di‐isocyanate, and trans‐2‐butene‐1,4‐diisocyanate. The latter has been reported previously(1,2)although never isolated and characterized; however, this has been achieved successfully in this study.

A Collagen/Vicryl (Polyglactin) composite membrane (developed for use in urinary tract surgery) has been incubated in cultures of radioactively labelled urinary tract pathogens vis Escherichia coli, Staphylococcus epidermidis, and Proteus mirabilis for up to 1h. For comparison, collagen film, Vicryl mesh, and a number of absorbable and nonabsorbable sutures were similarly tested. Following incubation, samples were also examined by scanning electron microscopy. Under the experimental conditions employed, only minimal adherence of the micro-organisms to the collagen coated Vicryl mesh, its two individual components, as well as Vicryl and nylon sutures was observed. Significantly greater numbers of bacteria, however, ahered to silk and Chromic Catgut. The results suggest that adherence of microorganisms to the prosthesis even in infected urine is unlikely to develop into a microcolony of bacteria. However, it should be emphasised that great care must be excercised when extrapolating from the in-vitro to the in-vivo situation.

Collagen/vicryl (Polyglactin) composite membrane has been used to repair full-thickness defects in the urinary bladder of rabbits. The material has been shown to be biodegradable, prevent leakage of urine, and is readily replaced by collagenous scar tissue lined with a urothelium. Regeneration of smooth nuscle has been observed in the repair area of some animals. The results suggest that such a material may well be of use to urologists wishing to augment contracted bladders or in the repair of bladder fistulae in human subjects, thereby avoiding the use of bowel or other material e.g. omentum.

Collagen coated vicryl mesh has been incubated with a series of urine collections from healthy and stoneforming patients. For comparison, collagen film, vicryl mesh, and a number of absorbable and non-absorbable sutures were similarly tested. Incubation in rabbit urine were also included in the study. Deposition of urinary salts, estimated qualitatively by electron microcopy, were observed on the collagen vicryl composite in approximately two thirds of the urines tested including rabbit urine. Those urines from patients with a high calcium excretion in particular caused urinary deposits on the material. Similar results were obtained with collagen film although the latter was not tested in rabbit urine. Considerably less deposits of urinary constituents were found with other absorbable materials such as vicryl mesh, vicryl sutures, and chromic catgut, whereas a higher proportion of concretions were found with the nonabsorbable sutures. The results indicate that urinary salt deposition may be a problem associated with collagen based composite materials after prolonged exposure to urine. It must, however, be emphasised that great care should be exercised when extrapolating any results obtained in-vitro to the in-vivo situation.

A composite membrane produced from collagen and vicryl mesh has been used to cover the kidney surface following partial nephrectomy in rabbits. The membrane readily held sutures, gave satisfactory haemostasis, and prevented leakage of urine. The experiments showed that the prosthesis biodegraded in less than twenty weeks. The only observed long-term effect of the material was thickening of the renal capsule. The results indicate that this membrane may be a suitable reparative materal for use in traumatised kidneys in humans.

A Vicryl (Polyglactin)/Collagen composite membrane has been developed for potential use in urinary tract surgery. The compatability of this membrane, together with its two individual components, collagen film and vicryl mesh, has been tested over a three week period in urine obtained from both healthy and from stone forming patients. The rate of degradation as indicated by changes in the mechanical strength was determined at regular intervals. In addition,absorbable suture materials such as plain catgut, chromic catgut, and vicryl were similarly tested; in the latter case, the breaking stress, and actual loss of weight of the material were compared. The whole series of experiments were then repeated in urine obtained from rabbits, the animal chosen for any future in vivo studies.

Various replicates of collagen substrata were prepared to study the attachment, growth and spreading of baby hamster kidney (BHK) cells. Cell attachment was measured in both the presence and absence of serum. Spreading and growth did not occur in the absence of serum. Attachment to fibrous collagen was less than that found with glass, rat-tail tendon collagen or films prepared from pepsin-solubilized collagen (PS-collagen). Incorporation of hyaluronate, heparin and protamine sulphate into the fibrous collagen and the acetylation of fibrous collagen had little effect. However, incorporation of chondroitin sulphate or chemical modification of fibrous collagen by either methylation or succinylation increased BHK cell attachment. In the absence of serum, the attachment to collagen, acetylated collagen and collagen composites was reduced. The reduction in attachment was marked with fibrous collagen and gelatin films, but less so with collagen composites, acetylated collagen, rat-tail tendon and PS-collagen films. Interestingly, attachment to succinylated collagen and methylated collagen was largely unaffected by the absence of serum, and possible reasons for this are discussed. Cell shape measurements showed decreased spreading of BHK cells on chemically modified collagen films, especially on gelatin films and dried PS-collagen gels. Cell shape and spreading on PS-collagen, rat-tail tendon collagen and collagen-composite films was found to be similar to that on fibrous collagen. BHK cell growth on fibrous collagen, chemically modified collagens, collagen composites, rat-tail tendon and PS-collagen films was similar to that found on plastic tissue culture substrate. Denaturation of fibrous collagen resulted in decreased growth, and BHK cell growth was markedly reduced on PS-collagen gels and dried gels.

The effects of 2.5, 5.0, 7.5 and 10 Mrad gamma-irradiation and ethylene oxide sterilization on collagen-coated vicryl mesh, on collagen film and vicryl mesh were investigated. No cytotoxic effects were observed towards either L929 cells or human fibroblasts with any of the treatments, even at the highest doses of irradiation. Although the rate of biodegradation and tissue reaction towards the test materials appeared to be relatively unaffected by ethylene oxide, the rate of breakdown in the lumbar muscles of laboratory rats was considerably increased by irradiation. Dose-dependent irradiation damage to the vicryl mesh was confirmed in vitro using viscometry and by an increase in the rate of hydrolysis in phosphate-buffered saline (PBS) at 37°C. Tensiometric studies on irradiated collagen films showed a dose-dependent reduction in both the break load and elongation before breaking. A small reduction in the break load and stretch to breaking was also observed following treatment with ethylene oxide. The findings presented favour ethylene oxide as a method of sterilization of both the composite membrane and its individual components. However, gamma-irradiation produced no toxic effects or adverse tissue reaction under the conditions described, and is more convenient to use. Hence, provided that the efficacy of the membrane would not be compromised by the higher rate of degradation, it could also be considered for sterilization of the material.

One- and 7-day-old specific pathogen-free chickens were artificially infected with a field isolate of Salmonella enteritidis, phage type 13A. At intervals up to 42 days of age, birds were killed and liver, lung, spleen, brain, yolk sac, testis or ovary, duodenum, jejunum, ileum, caecum and colon collected for culture.In chickens infected at one day of age and killed 1, 4 and 7 days pi all tissues were infected. Thereafter most non-intestinal tissues (74%) and intestinal tissues (92%) were positive for S. enteritidis.In chickens infected at 7 days of age, all tissues were positive 1 dpi. After post-inoculation day 1, a few non-intestinal tissues (15%) were positive for S. enteritidis while 38% of intestinal tissues were positive.

Studies on the effect of pH and ionic strength upon the activity of purified bovine testicular hyaluronidase have shown that the pH optimum for the hydrolysis of hyaluronic acid occurs at 5. 2 in the presence of, and at 6. 0 in the absence of NaCl. Hydrolytic activity towards various mucopolysaccharide and hyaluronate octasaccharide substrates was dependent upon the presence of strong electrolyte (LiCl, NaCl, KC1, CsCl, NaNO3 and Na2SO4), maximum activity being obtained at electrolyte strengths of 0. 2.Identical weights of sulphated and unsulphated mucopolysaccharides were hydrolysed at similar rates under optimal conditions, except that double chains of chondroitin 4-sulphate were hydrolysed at twice the rate of the other polysaccharides.Hydrolytic activity towards hyaluronate hexasaccharide was favoured at pH values below 5. 2 whereas trans-glycosylation activity was favoured at higher pH. Hyaluronate tetrasaccharide was neither a substrate for the hydrolytic or transglycosylation activity, nor was it an inhibitor of the enzymic hydrolysis of hyaluronic acid.No conformational change in hyaluronic acid was detected by CD-spectroscopy in the presence of varying concentrations of salt and the collective results suggest that the salt effect is exerted on the enzyme rather than on the substrate.

Summary No ideal dural grafting material is currently available. Many materials have been evaluated in this role, and for many neurosurgeons cadaveric human lyophilized dura has been popular. Recently this material has been putatively associated with Creutzfeldt-Jakob disease.

Lung, trachea and bursa of Fabricius were collected from broilers between 14 and 49 days of age from eight flocks with varying levels of mortality and air sac disease (air sacculitis often accompanied by pericarditis and perihepatitis). These tissues were screened for the presence of Cryptosporidia sp. Bursal cryptosporidial infection was present in two flocks between 21 and 42 days of age. These two flocks had a high incidence of air sac disease and the highest overall mortality of the eight flocks between 15 and 49 days of age. Weekly mortality rates increased and remained elevated with the onset and persistence of cryptospordial infection. Mortality was lower when no crypto-spordia were found. The incidence of air sac disease did not decrease when cryptosporidia were no longer present.

Thein vivo breakdown of collagen-vicryl composites (types 9 and 12) was followed in rabbit ear chambers over a period of 5 weeks. In this time the implants were incorporated into the granulation tissue growing in the chambers. Materials that were sterilized by gamma irradiation were resorbed faster than those sterilized with ethylene oxide or disinfected with alcohol, which suggests that irradiation weakened the material. Histological observation revealed that the collagen component had disappeared from all the composites by day 35 and the surrounding tissue showed a mild foreign-body reaction.

A series of experiments have been carried out in-vitro in order to assess the possibility of using a collagen membrane in the repair of various sections of the urinary tract following operative surgery such as the removal of a stone from the ureter. The collagen film has been tested for its compatability with urine, its ability to prevent leakage of fluid in a simulated wound in-vitro and for its ability to withstand any degradative effect of liver and kidney homogenates. The material was not significantly degraded by either urine or by tissue homogenates and was able to prevent leakage of fluid under the experimental conditions employed. Although some slight build-up of calcium and some trace elements took place after incubation in urine over a six-day period this was not significant. On the basis of the results obtained it has been decided to proceed to in-vivo trials on rabbits using the collagen membrane. The possibility of using such a material in partial nephrectomy operations is discussed.

A study of neonatal and perinatal mortality rates based on weight and gastational age for white single births in a middle class population receiving private medical care showed that mortality rates decrease until 40 weeks of gestation and then begin to rise again after 43 weeks of gestation. The mortality rates do not change significantly with increasing weight after 3,750 gm (7 lb). A plan, modified from others, classifies newborn infants into risk groups on the basis of weight-gestational age. In addition to defining high-risk newborn infants, a medium-risk group is identified whose special needs should be met.

Collagen-coated Vicryl® mesh was assessed as a prosthetic repair material in the oesophagus of growing piglets. In a group of six piglets (group A), a full thickness defect was created in the oesophagus without fully transecting the organ. The removed tissue was subsequently replaced with a patch of collagen-coated Vicryl mesh. Animals were killed at 4 weeks and in the five surviving piglets the prosthesis had been replaced by host scar tissue with a normal epithelial lining. Two further groups of six piglets (groups B and C) were used as controls. In group B the oesophagus was either partly transected (four animals) or completely transected (two animals) and an anastomosis was performed, whereas in group C a 2.5-cm length of oesophagus was removed so that the anastomosis was performed under tension. In group B, all six piglets survived, whereas in group C, where the anastomosis was performed under tension, only two piglets survived. Microscopic and macroscopic examination of all groups showed that the collagen-coated Vicryl prosthesis was replaced by scar tissue; moderate stenosis was observed in only one animal in group A. Collagen-coated Vicryl mesh may be used either to reinforce an anastomosis performed under tension or may find use in tubular form to bridge the gap between the two ends of the oesophagus to be joined. It is envisaged that such a material may find applications in the treatment of oesophageal atresia.

A study was undertaken to determine the incidence of subsequent handicaps in children who were of very-low-birth weight. From 1968 through 1976, 59 infants with birth weights of 1000 grams or less, and less than 72 hours old upon admission, were discharged from the Neonatal Intensive Care Center at the University of Oregon Health Sciences Center. Forty-three children, thirty-two girls, and eleven boys, were seen in follow-up for psychological testing. Their mean birth weight was 912 grams, and mean gestational age was 28.6 weeks. Seven children were small for gestational age (SGA), 36 were appropriate for gestational age (AGA). Their mean age was 3.7 years (range 6 months to 9 years). Six children (14%) have cerebral palsy, two seizure disorders, one has hydrocephalus, and one has impaired vision due to retrolental fibroplasia. Psychological testing was incomplete in two children, one has cerebral palsy and developmental delay, the other appears normal. The mean intelligence quotient for 41 children is 92.1. Thirty-two (78%) have scores greater than 80. Six (14.6%) have quotients between 70 and 80, and three (7.3%) are mentally retarded with intelligence quotients of less than 70. The mean intelligence quotient of the 7 children who were SGA is 97.1; of these, one child has cerebral palsy.We believe these data reflect the improving prognosis of infants with very-low-birth weight.