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Biomedical subjects

A Gilbert

Publications and source records attributed to A Gilbert.

At least 55 records · Page 3Linked to original sources

Molecular and cellular mechanisms governing the ligand-specific and non-specific steps of insulin receptor internalization.

The surface events leading to insulin-induced internalization of its specific receptor can be subdivided in three major steps: the first step consists in the surface redistribution of the receptor from the villous to the non-villous region of the cell surface, it is ligand-specific, depends on kinase activation and phosphorylation of tyrosines 1146, 1150 and 1151, and consists in the relief of a constraint immobilizing the receptor on microvilli; the second step is characterized by the shift of the insulin-receptor complex in the plane of the membrane allowing it to get access to the nonvillous domain of the cell surface where internalization gates (clathrin-coated pits) are located; this stage is controlled, at least in part, by the transmembrane domain of the molecule and its flanking amino acids; the third step corresponds to the segregation of the insulin-receptor complex in clathrin-coated pits, this step is relatively non-specific and is governed by well defined signal sequences present in the juxtamembrane domain of the cytoplasmic segment of the b-subunit. These surface events are then automatically followed by the entry of the insulin receptor inside the cells through the formation of clathrin-coated vesicles, in its subsequent association with endosomes which acidic pH allows insulin dissociation from its receptor and the sorting of the receptor and the hormone in different directions: insulin is targetted to lysosomes to be degraded while the receptor is recycled back to the cell surface to be reused. This complex process does not seem to be involved in the transmission of the biological signal of the hormone. Nevertheless, it is initiated and controlled by insulin and results in the intracellular degradation of insulin and in the modulation of the number of surface insulin receptors. Thus, even if it does not directly participate in insulin signaling, insulin receptor internalization plays a crucial role in the control of insulin action.

Animals↗

Gastrocystoplasty: technical and metabolic characteristics of the most versatile childhood bladder augmentation modality.

The authors report on 23 patients who underwent complex continent urinary reconstructions, made successful by the selection of gastrocystoplasty as the chosen augmentation modality. The mean patient age was 6.1 years, and the mean weight was 17.9 kg. The minimum follow-up period was 1.5 years. The bladder capacity increased from a preoperative mean of 77.8 +/- 52.2 (SD) mL to a postoperative mean of 303.5 +/- 117.4 mL (P < .000001). No adverse effects on renal function or serum electrolyte composition were encountered, and there were no instances of acidosis or alkalosis. Continence was achieved in 91% of patients. In two patients (0.9%), hematuria-dysuria developed; one case was extremely mild. The other occurred only during a period of severe oliguria and resolved after transplantation. Gastrointestinal complications were minimal. Five patients had end-stage renal disease at the time of reconstruction and have since had successful transplantation. Gastrocystoplasty is particularly applicable to the pediatric population because of its unique anatomic and metabolic characteristics, which bestow tremendous versatility.

Acidosis↗

Hook-nail deformity. Surgical treatment with a homodigital advancement flap.

Sixteen patients presenting 18 hook-nail deformities have been treated by the advancement of a homodigital island flap. With an average follow-up of 31 months; Results were considered good or excellent in seven cases, fair in seven and poor in four. Six cases, although improved, had a marked recurrence of the deformity, six had a partial recurrence and six had almost no recurrence. Patient satisfaction was limited as the finger still had a short nail and a square shape.

Adult↗

Relative microbial resistance of gastric, ileal and cecal bladder augmentation in the rat.

PURPOSE: Bladder resistance to bacterial infection after gastrocystoplasty, ileocystoplasty and cecocystoplasty was investigated in the rat. MATERIALS AND METHODS: Bladders were infected with Escherichia coli 6 to 13 months after augmentation and urine culture was obtained weekly for 3 months. RESULTS: No differences were observed in the number of infected animals within each group or electrolyte data among groups. The number of animals infected after surgery but before E. coli challenge was lowest in the gastrocystoplasty group. Bladder stones formed only in ileocystoplasty and cecocystoplasty groups. No group had a change in urinary pH. CONCLUSIONS: Gastrocystoplasty may be associated with a lower incidence of spontaneous infection and stone formation. An aggressive infection protocol may have masked differences in susceptibility to infection. Since urinary pH was unchanged after gastrocystoplasty, use of the rat may not be appropriate for augmentation studies.

Animals↗

Congenital pseudarthrosis of the tibia. Long-term followup of 29 cases treated by microvascular bone transfer.

The authors show that vascularized fibular transplantation is the safest technique to treat congenital pseudarthrosis of the tibia. Results of transplantation in 29 patients reveal that the rate and speed of healing were superior to those of any other published method, and the final outcome at maturity was generally acceptable. In addition, the technique allows secondary lengthening procedures to be done. Various factors, such as age at first fracture, age at operation, gender, and type of fixation, did not appear to influence the outcome significantly.

Adolescent↗

Obstetrical palsy: early treatment and secondary procedures.

Obstetrical palsy has been described since a long time. Unfortunately, until the last 20 years, few options were available to correct its sequelae. During the last two decades, there has been a regain of interest because of the possibility to microsurgically repair these lesions. Tassin in 1984 demonstrated that babies who have no recovery of the biceps function by three months of age should be operated without delay. At brachial plexus exploration, in the presence of neuroma, nerve grafting is usually necessary. In cases of root avulsion, internal or external neurotization should be performed depending on the severity of the lesions. Physiotherapy and long-term follow-up of these patients are primordial to prevent joint ankylosis and to identify the patients who will benefit from secondary surgery. Our results are presented either after early treatment or after secondary procedures. These results justify aggressive management of obstetrical brachial plexus palsy because of children's great capacity for regeneration and accommodation.

Ankylosis↗

Experimental and clinical study of the effect of naftidrofuryl on the recovery from peripheral nerve lesions.

After primary repair of lesions of nerves and vessels, patients who were administered a vasoactive drug, naftidrofuryl, postoperatively, had a better functional recovery than untreated patients. Evidence for the favourable effect of the drug on nerve regeneration was first obtained from experiments in the rat. The sciatic nerve was transected and repaired with standard microsurgical techniques. Results were evaluated by electromyography and histology. Data indicated that treated animals had better motor responses and distal latency than untreated rats. Fibre counts showed a greater number of nerve fibres in the distal stump of treated animals. The clinical study was undertaken in cases of carpal tunnel syndrome with muscle atrophy. Assessment was performed by electrophysiology: motor and sensory conduction was studied. Data showed that all treated patients recovered totally or partially from the thenar atrophy they presented before operation, whereas thenar atrophy persisted in 37% of the patients receiving placebo. In conclusion, naftidrofuryl has an experimentally and clinically favourable effect on nerve regeneration and on muscle trophicity, but the mechanism of action of this drug is not known.

Aged↗

Upper tibial corticocancellous flap anatomy study (19.2.93).

A cortico-cancellous flap from the anterolateral aspect of the upper third of the tibia was presented. Sixty lower limbs of "fresh" cadavers were dissected. The vascular bundle includes the anterior tibial artery and its recurrent collateral branches and recurrent and musculoperiosteal arteries. The flap is harvested with the interosseous membrane and can be used either free or predicled. We used this flap for two patients suffering from pseudarthrosis. Long range clinical and radiological results are good.

Adult↗

Renal transplantation into the dysfunctional bladder: the role of adjunctive bladder reconstruction.

A retrospective review of pediatric renal transplantation at 3 centers identified 9 patients who had undergone major bladder reconstruction. Seven patients underwent bladder augmentation (5 gastric, 1 colonic, 1 ureteral) and 2 received gastric neobladders. Six patients required Mitrofanoff neourethras. Patient survival was 100% with initial graft survival of 56% during a mean followup of 29.4 months. Eight patients (89%) are presently dialysis-free with functioning allografts and all 9 (100%) are continent of urine. We conclude that renal transplantation and reconstruction to ensure continence are justifiable in even the most anatomically compromised children with end stage renal disease. It is essential that the pediatric urologist should have an integral role in the management of such cases.

Adult↗

Vaginal reconstruction: critical technical principles.

Childhood vaginal anomalies are frequently encountered, often in association with significant anorectal or urinary tract abnormalities. As a result, reconstruction poses a number of technical challenges. We maintain that the best results are achieved by single stage perineal reconstruction. The primary goal of achieving a functional and cosmetically adequate vagina must not be at the expense of the optimal repair of associated urinary and anorectal abnormalities. In addition, since these repairs are performed early in childhood, vaginal growth is an issue that further limits the choice of reconstructive technique. We present a series of successful vaginal reconstructions in complex cases and an outline of the principles of surgical care.

Abnormalities, Multiple↗

Surgical implications of genitourinary tract anomalies in patients with imperforate anus.

Genitourinary anomalies in patients with imperforate anus are a frequent source of significant morbidity. We report a retrospective study of 64 genitourinary procedures performed on 23 patients. Renal, collecting system, bladder and perineal anomalies were encountered in 65%, 83%, 87% and 65% of these complex cases, respectively. A total of 70% of the patients required intermittent catheterization due to bladder dysfunction. Surgical alternatives, complications of management and functional outcomes are reviewed in detail. Genitourinary reconstruction is best undertaken as an integral part of imperforate anus reconstruction. Failure to do so results in the loss of surgical alternatives, unnecessary reoperative procedures and compromised outcomes.

Abnormalities, Multiple↗

Congenital pseudarthrosis of the forearm: treatment of six cases with vascularized fibular graft and a review of the literature.

Six cases of pseudarthrosis of the forearm are reported. One involved only the radius, one the ulna alone, and four both forearm bones. There was associated neurofibromatosis in five cases. All the cases were treated by wide resection and free vascularized fibular graft. In two cases, a single-bone forearm was created. In all cases, good results were achieved, with moderate forearm shortening. The literature suggests electrical stimulation, corticoperiosteal graft, osteotomy of the involved bone, and free vascularized bone grafting as treatment alternatives. Vascularized free bone grafting appears to be more successful than other treatments. The use of microsurgical sutures permits this treatment in young patients.

Adolescent↗

Two steps of insulin receptor internalization depend on different domains of the beta-subunit.

The internalization of signaling receptors such as the insulin receptor is a complex, multi-step process. The aim of the present work was to determine the various steps in internalization of the insulin receptor and to establish which receptor domains are implicated in each of these by the use of receptors possessing in vitro mutations. We find that kinase activation and autophosphorylation of all three regulatory tyrosines 1146, 1150, and 1151, but not tyrosines 1316 and 1322 in the COOH-terminal domain, are required for the ligand-specific stage of the internalization process; i.e., the surface redistribution of the receptor from microvilli where initial binding occurs to the nonvillous domain of the cell. Early intracellular steps in insulin signal transduction involving the activation of phosphatidylinositol 3'-kinase are not required for this redistribution. The second step of internalization consists in the anchoring of the receptors in clathrin-coated pits. In contrast to the first ligand specific step, this step is common to many receptors including those for transport proteins and occurs in the absence of kinase activation and receptor autophosphorylation, but requires a juxta-membrane cytoplasmic segment of the beta-subunit of the receptor including a NPXY sequence. Thus, there are two independent mechanisms controlling insulin receptor internalization which depend on different domains of the beta-subunit.

Amino Acid Sequence↗

Trial of an intervention to reduce chronic benzodiazepine use among residents of aged-care accommodation.

BACKGROUND: Many residents of aged-care accommodation are chronic users of benzodiazepines. This pattern of use contradicts current guidelines and may adversely affect residents. It was hypothesised that a lasting reduction in benzodiazepine use could be achieved through a programme which involved prescribers, residents and caregivers in the change process. AIM: To demonstrate that an intervention which involved education and relaxation training for patients, and education of prescribers and caregivers, could reduce levels of chronic benzodiazepine use among residents of an aged-care facility. METHODS: Two aged-care facilities from metropolitan Adelaide were chosen; one received the intervention, the other was a no-intervention comparison. Pre-test, post-test and follow-up interviews were conducted with 60 residents: 27 from the intervention setting and 33 from the comparison setting. Residents at the intervention setting were provided with relaxation skills training, and their medical practitioners and caregivers were provided with information about alternative strategies for managing sleep disturbance. Outcome measures were: the proportion of residents using benzodiazepines, total medication use, cognitive performance, emotional responsiveness, subjective health and sleep ratings and an index of well-being. RESULTS: The proportion of participants in the intervention condition who used benzodiazepines declined significantly (from 70% to 35%); the reduction was maintained over the subsequent three months. No adverse consequences were associated with cessation of benzodiazepine use; there was improvement in emotional responsiveness among those who ceased benzodiazepine use. This structured intervention strategy is a useful approach for reducing levels of chronic benzodiazepine use among residents of aged-care accommodation.

Affect↗