Fibrin glue for securing the mesh in laparoscopic totally extraperitoneal inguinal hernia repair: a study with a 40-month prospective follow-up period.

BACKGROUND: Anchoring the mesh in laparoscopic totally extraperitoneal groin hernia repair (TEP) with human fibrin glue has theoretical advantages. However, these have been supported and reported previously only in animal studies. Before the initiation of large patient trials, the authors wanted to confirm the feasibility, assess the costs, and rule out any flagrant short- and long-term adverse effects of fibrin glue usage in a small series of patients. METHODS: Nine consecutive TEP repairs with fibrin glue mesh fixation were performed. The perioperative and postoperative outcomes at 1, 16, and 40 months were compared with those for a control group of 96 stapled repairs. RESULTS: Gluing was easy and is less expensive than stapling. No fibrin glue-related adverse effects were found. The overall outcome was similar to that for stapled repairs, with no indication that the glued repairs were inferior. CONCLUSIONS: Fibrin glue seems to be a reasonable, feasible, and maybe even competitive alternative to the standard tissue-penetrating mesh fixation. The results of this study justify launching larger trials.

Amitriptyline-induced loss of tight junction integrity in a human endothelial--smooth muscle cell bi-layer model.

Tricyclic antidepressants can, when taken in overdose, cause serious pulmonary failure such as the adult respiratory distress syndrome (ARDS). In this study we have examined the effects of some tricyclic antidepressants (amitriptyline, imipramine, nortriptyline and desipramine) on the viability and morphology of human endothelial and smooth muscle cells derived from umbilical cord. Effects of amitriptyline on endothelial cell fluidity, as well as permeability changes to an endothelial-smooth muscle cell bi-layer, were also studied. The tricyclic antidepressants induced acute, sub-lethal toxicity in both cell types above 100 microM as assessed by the MTT reduction assay. Morphological changes were also observed at these concentrations. Such changes were, however, absent at 33 microM and below. Amitriptyline did, however, cause a concentration-dependent fall in the electrical resistance of an endothelial-smooth muscle cell bi-layer, with significant effects already evident at 33 microM. All of these observed effects were fairly rapid and appeared within 5-15 min of exposure. The rapidity of these permeabilisation effects suggests potential membrane perturbations, since tricyclic antidepressants are lipophilic molecules with affinity for cell membranes. However, fluorescence anisotropy measurements showed no significant difference in membrane fluidity between amitriptyline-treated and control endothelial cells. Collectively, these data point to specific mechanisms of action of amitriptyline, and probably also the other tricyclic antidepressants studied, on endothelial permeability, which is a hallmark of ARDS. The data suggest that increased endothelial permeability could be due to impaired tight junction function.

Amitriptyline-induced release of endothelin-1 in isolated perfused and ventilated rat lungs.

We have previously shown that tricyclic antidepressants can induce vaso- and bronchoconstriction as well as oedema formation in isolated perfused lungs. This is an effect similar to that seen clinically in adult respiratory distress syndrome. In order to investigate whether endothelin can be a mediator of this reaction, isolated perfused rat lungs were exposed to 0.1 mM amitriptyline via the pulmonary circulation, perfusate was collected and endothelin-1 present in the perfusate and lavage fluids was determined by radioimmunoassay. A significant increase in perfusate concentration of endothelin-1 was noted, with the highest release seen within the first 10 min. of exposure. Histamine and thromboxane have also been proposed as mediators in induction of adult respiratory distress syndrome. However, no increased amounts of these mediators were detected in the perfusate. Experiments where lungs were exposed to exogenous endothelin-1(0.1-1 nmol), both via the perfusate and via intratracheal instillation were conducted. Similar effects as observed with amitriptyline (0.1 mM) on lung function and perfusion flow were detected. In conclusion, the detection of endothelin-1 release in our lung model proposes a role for endothelin-1 in amitriptyline-induced vaso- and bronchoconstriction and possibly in adult respiratory distress syndrome type reaction. Further studies with this model are interesting in order to elucidate mechanisms behind the complex issue of adult respiratory distress syndrome-induction.

Characterization of a silicon transporter gene family in Cylindrotheca fusiformis: sequences, expression analysis, and identification of homologs in other diatoms.

The transport of silicon is an integral part of the synthesis of the silicified cell wall of diatoms, yet knowledge of the number, features, and regulation of silicon transporters is lacking. We report the isolation and sequence determination of five silicon transporter (SIT) genes from Cylindrotheca fusiformis, and examine their expression patterns during cell wall synthesis. The encoded SIT amino acid sequences are highly conserved in their putative transmembrane domains. Nine conserved cysteines in this domain may account for the sensitivity of silicon uptake to sulfhydryl blocking agents. A less conserved C-terminal domain is predicted to form coiled-coil structures, suggesting that the SITs interact with other proteins. We show that SIT gene expression is induced just prior to, and during, cell wall synthesis. The genes are expressed at very different levels, and SIT1 is expressed in a different pattern from SIT 2-5. Hybridization experiments show that multiple SIT gene copies are present in all diatom species tested. From the data we infer that individual transporters play specific roles in silicon uptake, and propose that the cell regulates uptake by controlling the amount or location of each. The identification of all SIT genes in C. fusiformis will enhance our understanding of the mechanism and control of silicon transport in diatoms.

Acute lung failure induced by tricyclic antidepressants.

Overdosing of several drugs, such as tricyclic antidepressants, salicylates, and opiates, is known to induce effects like those seen in patients with adult respiratory distress syndrome. By exposing isolated perfused and ventilated rat lungs via the perfusate to six different tricyclic antidepressants (amitriptyline, nortriptyline, imipramine, desipramine, mianserine, and maprotiline), we investigated possible effects on ventilation (conductance and dynamic compliance), lung perfusion flow, and edema formation. The effects of these substances were pronounced and appeared within 15 min after exposure. Amitriptyline was studied in greater detail and caused a dose-related (0.01-1.0 mM) reduction in ventilation and perfusion flow. At the highest drug concentration pronounced lung edema was observed. Morphological studies were conducted with a transmission electron microscope. The microscopic preparations showed dose-related edema (amitriptyline 0.1 and 1.0 mM). The effects noted in our experimental studies are similar to those described in patients who have taken an overdose of tricyclic antidepressants. This emphasizes the possibility of a noncardiogenic edema component in these patients.

The primary structure of NG2, a novel membrane-spanning proteoglycan.

The complete primary structure of the core protein of rat NG2, a large, chondroitin sulfate proteoglycan expressed on O2A progenitor cells, has been determined from cDNA clones. These cDNAs hybridize to an mRNA species of 8.9 kbp from rat neural cell lines. The total contiguous cDNA spans 8,071 nucleotides and contains an open reading frame for 2,325 amino acids. The predicted protein is an integral membrane protein with a large extracellular domain (2,224 amino acids), a single transmembrane domain (25 amino acids), and a short cytoplasmic tail (76 amino acids). Based on the deduced amino acid sequence and immunochemical analysis of proteolytic fragments of NG2, the extracellular region can be divided into three domains: an amino terminal cysteine-containing domain which is stabilized by intrachain disulfide bonds, a serine-glycine-containing domain to which chondroitin sulfate chains are attached, and another cysteine-containing domain. Four internal repeats, each consisting of 200 amino acids, are found in the extracellular domain of NG2. These repeats contain a short sequence that resembles the putative Ca(++)-binding region of the cadherins. The sequence of NG2 does not show significant homology with any other known proteins, suggesting that NG2 is a novel species of integral membrane proteoglycan.

The expression of NG2 proteoglycan in the developing rat limb.

NG2 is a chondroitin sulfate proteoglycan previously found to be expressed by glial progenitor cells of the O2A lineage. We have examined the expression of NG2 in the developing rat limb by immunohistochemistry and northern blot analysis. Staining of embryonic day 14 (E14) rat limb bud sections with polyclonal and monoclonal anti-NG2 antibodies reveals reactivity in the precartilaginous mesenchymal condensation. The staining intensity increases with the differentiation of chondrocytes until E16. NG2 staining is not detected in the mature hypertrophic chondrocytes of E17 and postnatal day 3 (P3) limbs even after treatment of the sections with hyaluronidase or collagenase. Immuno-precipitations with anti-NG2 antibody using 125I-labeled limb cells in culture showed a 400 to 800 x 10(3) Mr proteoglycan species with a core protein size of 300 x 10(3) Mr, comparable to NG2 from O2A cells and neural cell lines. Northern blot analysis reveals the expression of an 8.9 kb mRNA in E16 limbs and at a lower level in P1 cartilage. The northern blot analyses also show that NG2 is distinct from the large aggregating proteoglycan of the cartilage. Our results indicate that in the developing limb cartilage, as in the differentiating oligodendrocytes, NG2 is present on immature cells in the process of differentiating, but its expression is downregulated as terminal differentiation of chondrocytes takes place.

Interaction of the NG2 chondroitin sulfate proteoglycan with type VI collagen.

The NG2 chondroitin sulfate proteoglycan is a membrane-associated molecule of approximately 500 kD with a core glycoprotein of 300 kD. Both the complete proteoglycan and a smaller quantity of the 300-kD core are immunoprecipitable with polyclonal and monoclonal antibodies against purified NG2. From some cell lines, the antibodies coprecipitate NG2 and type VI collagen, the latter appearing on SDS-PAGE as components of 140 and 250 kD under reducing conditions. The immunoprecipitation of type VI collagen does not seem to be due to recognition of the collagen by the antibodies, but rather to binding of the collagen to NG2. Studies on the NG2-type VI collagen complex suggest that binding between the two molecules is mediated by protein-protein interactions rather than by ionic interactions involving the glycosaminoglycans. Immunofluorescence double labeling in frozen sections of embryonic rat shows that NG2 and type VI collagen are colocalized in structures such as the intervertebral discs and arteries of the spinal column. In vitro the two molecules are highly colocalized on the surface of several cell lines. Treatment of these cells resulting in a change in the distribution of NG2 on the cell surface also causes a parallel change in type VI collagen distribution. Our results suggest that cell surface NG2 may mediate cellular interactions with the extracellular matrix by binding to type VI collagen.

The prevalence and the etiology of the initial dummy- and finger-sucking habit.

The prevalence of dummy- and finger-sucking habits, or malocclusions of the type that may be associated with sucking habits, was examined in three different groups: Group A--415 small children from Mnene, Zimbabwe; group B--20 skulls from the Schreiner Collections, Anatomical Institute, Oslo, exhibiting intact deciduous dentitions. The skulls are mainly from the period A.D. 1000 to 1500 and were found in Scandinavia. Group C consisted of 280 young Swedish children. The study indicates that dummy- and finger-sucking habits occur infrequently among the African children other than as a symptom of a disturbance in the normal feeding and/or care in other respects. The investigation of the medieval skull material supports a similar situation among these Scandinavian children. In Sweden most infants are dummy- or finger-suckers. The authors introduce an explanation for the development of the initial sucking habits.

[Improved health in Zimbabwe's rural areas as a result of the rural development project]. / Bättre hälsa på Zimbabwes landsbygd genom byutvecklingsprojekt.

PIP: A rural development project carried out in Southern Zimbabwe for 5 years was aimed at improving nutrition, combatting diseases, educating villagers about proper hygiene, improving water quality, and assessing the development and nutritional status of children under 5. The community investigated consisted of 10,000 people or 1,439 families with an average of 7 persons per family. The main staple of their diet was maize, and malnutrition was prevalent. Water holes infested with bilharzia were the source of drinking water for both man and animal. The project succeeded in vaccinating 90% of preschool children against whooping cough, diphtheria, tetanus, polio, measles, and tuberculosis. A control district was chosen to compare the developmental data obtained by the Cole Slide Rule Calculator of 229 children under 5 with those of 242 children in the project. Malnutrition was studied in 200 children hospitalized in the children's ward of a district hospital, 1/3 of whom were less than 1 year old. Gastroenteritis, giardiasis and amebiasis were prevalent among them (37%), as were upper respiratory infections (27%), pneumonia (12%), and skin infections (7%). Nonspecific gastroenteritis was found in 86% of children under 2. Most over 2 were severely undernourished. A nutritional rehabilitation village called Hutano Village was established in 1982 to function as a nutritional center, staffed by a full-time health worker and an assistant. In the 1st 9 months of its existence, 114 children were taken in, and the mothers received instruction in vegetable gardening, raising chickens and rabbits, hygiene, and family planning. The average attendance runs to 25 children and 15 to 17 mothers. In spite of successful medical intervention in malnutrition cases, the relapse of children into an undernourished state remains a difficult issue, whose cause lies in inadequate water supply, poor soil, lack of resources, and low family socio-economic status.^ieng