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At least 91 records · Page 5Linked to original sources

[Plastic surgery of the abdominal wall in laparocele in a patient with previous kidney transplant].

The authors report the case of a patient undergoing kidney transplant from a non-related but compatible living donor who subsequently developed a voluminous incisional hernia affecting almost the entire small intestine in the right iliac fossa, the site of earlier surgery. After having analysed the problems involved when a transplant patient requires further surgery owing to the chronic administration of drugs, the authors describe the case. The patient was treated using the insertion of a prolene graft and remodelling the abdominal wall in correspondence with the lower quadrants using abdominoplasty without repositioning the umbilicus.

Abdominal Muscles↗

Inappropriate discharges from an intravenous implantable cardioverter defibrillator due to T-wave oversensing.

This report describes the clinical management of 2 patients with ventricular fibrillation (VF) who received inappropriate shocks from an implantable cardioverter defibrillator (ICD) due to T-wave oversensing. Cardiac sarcoidosis was confirmed as the underlying heart disease in 1 patient and idiopathic dilated cardiomyopathy in the other. Within 2 months after ICD implantation, both patients received several inappropriate shocks during sinus rhythm. Stored electrograms showed decreased R-wave amplitudes and increased T-wave amplitudes. The ICD sensed both R- and T-waves as ventricular activation, which met the rate criteria for VF treatment. Reprogramming the sensing threshold in association with administration of a drug to slow the heart rate decreased the incidence of the inappropriate shocks in both patients, but these palliative measures did not completely suppress the inappropriate shocks. To avoid T-wave oversensing, the repositioning or adding of a sensing lead is required. The potential risk of T-wave oversensing in ICD patients who have small R-wave amplitudes should be recognized.

Adult↗

Analysis of HIV-2 RT mutants provides evidence that resistance of HIV-1 RT and HIV-2 RT to nucleoside analogs involves a repositioning of the template-primer.

Mutations that confer resistance to nucleoside analogs do not cluster around the deoxynucleotide triphosphate (dNTP) binding site. Instead, these mutations appear to lie along the groove in the enzyme where the template-primer binds. Based on such structural data and on complementary biochemical analyses, it has been suggested that resistance to nucleoside analogs involves repositioning of the template-primer. We have prepared mutations in HIV-2 RT that are the homologs of mutations that confer resistance to nucleoside analogs in HIV-1 RT. Analysis of the behavior of HIV-2 RT mutants (Leu74Val, Glu89Gly, Ser215Tyr, Leu74Val/Ser215Tyr and Glu89Gly/Ser215Tyr) in vitro confirms the results obtained with HIV-1 RT: resistance is a function of the length of the template overhang. These analyses also suggest that the homolog in HIV-2 RT of one of the mutations that confers resistance to AZT in HIV-1 RT (Thr215Tyr) confers resistance by repositioning of the template-primer.

DNA Primers↗

MR-appearance of the pituitary gland before and after resection of pituitary macroadenomas.

Pituitary macroadenomas can cause severe compression and displacement of the pituitary gland. This study was undertaken to determine the value of contrast administration for the detection of the pituitary gland in patients with pituitary macroadenomas, to evaluate the preoperative location and configuration of the pituitary gland and to describe its postoperative changes after tumour resection. Preoperative and postoperative MR imaging examinations of 30 patients with histologically proven pituitary macroadenomas were retrospectively evaluated. The examinations were performed on a 1.5 T unit, by obtaining T1-weighted sagittal and coronal images after administration of gadopentetate dimeglumine. On preoperative MR images, contrast administration increased the detectability of the anterior lobe from 30% to 80%. Depending on the size and extension of the adenoma, the pituitary gland was displaced to the suprasellar space (53%) and/or deformed to a club-shaped (27%) or sickle-shaped (47%) configuration. In six patients, the sickle-shaped pituitary gland was interposed between the cavernous sinus and the adenoma ('rim-sign'), which was seen only on gadopentetate dimeglumine-enhanced images. In these cases, there was no infiltration of the cavernous sinus at surgery. Postoperatively, descent of the pituitary gland was found in 63%, and reexpansion in 54%. We conclude that contrast administration improves the detectability of the pituitary gland on preoperative MR images, and that the displacement and deformation of the pituitary gland depend on the size, location and extension of the adenoma. Preoperatively, demonstration of the pituitary gland interposed between the cavernous sinus and the adenoma ('rim-sign') is a very useful sign for exclusion of cavernous sinus infiltration, best seen on contrast-enhanced coronal MR images. The normal postoperative changes of the pituitary gland after tumour resection include repositioning and re-expansion.

Adenoma↗

A peripheral protein associated with the cis-Golgi network redistributes in the intermediate compartment upon brefeldin A treatment.

Human autoantibodies offer unique tools for the study of cellular constituents since they usually recognize highly conserved components, the most difficult to detect due to their low immunogenicity. The serum from a patient with Sjögren's syndrome (RM serum) showing a very high reactivity to the Golgi complex has been shown to immunoprecipitate and to immunodetect by Western blotting experiments a protein mol wt 210,000 (p210) that was shown to be peripheral and cytoplasmically disposed. A close examination of the p210 labeling revealed some differences with Golgi markers: RM serum staining was slightly more extensive than several Golgi markers and showed a discontinuous or granular appearance. Nocodazole induced a specific and early segregation of many p210-associated vesicles or tubules from Golgi apparatus. Upon brefeldin A treatment, p210 did not redistribute in the ER as did other Golgi proteins. In contrast, it exhibited a vesicular pattern reminiscent to that displayed by proteins residing in the intermediate compartment. Double staining immunofluorescence using the RM serum and the marker of the intermediate compartment, p58, revealed segregation of both proteins in control conditions but colocalization in BFA-treated cells. We have further demonstrated by combining different drug treatments that p210-containing elements in brefeldin A-treated cells belong indeed to the intermediate compartment. Experiments on brefeldin A recovery suggested that these p210 elements might play a role in reformation and repositioning of the Golgi apparatus. Ultrastructural localization performed by immunoperoxidase staining allowed us to establish that p210 interacted with the external side of an abundant tubulo-vesicular system on the cis side of the Golgi complex which extended to connecting structures and vesicles between saccules or stacks of cisternae, p210 appears to be a novel protein residing in the cis-Golgi network that may cycle between the Golgi apparatus and the intermediate compartment.

Autoantigens↗

Changes in signs and symptoms following temporomandibular joint disc repositioning surgery.

Fifty-one subjects with documented intra-articular pathology refractory to non-surgical therapy underwent temporomandibular joint (TMJ) disc repositioning surgery. Following surgery, subjects were evaluated for 6 months to 6 years by clinical examinations and questionnaires at designated times, and by postsurgical joint imaging. Significant decreases were noted in pain (headache, TMJ pain, ear pain, and neck/shoulder pain), the incidence of joint sounds and locking, and the presence of dietary restrictions. However, 35% of the subjects continued to have residual TMJ pain, and a similar percentage continued to need periodic nonsteroidal anti-inflammatory drugs for analgesia. Some degree of dietary restriction remained in approximately 50% of the subjects, and joint sounds persisted in a similar percentage following surgery. Mean mouth opening was improved by 8 mm, although lateral movements were increased by less than 0.5 mm. Surgery did not decrease the occurrence of jaw deviation, and disc position was unchanged in 86% of the joints imaged at an average of 2 years following surgery. Although TMJ disc repositioning surgery significantly improved pain and dysfunction in TMJ surgery patients, the improvement in disc position was not maintained in most subjects following surgery.

Adolescent↗

Late traumatic dislocation of laser in situ keratomileusis flaps.

We present 2 patients with late traumatic laser in situ keratomileusis flap dislocation 8 months and 17 months after surgery. One patient had a sharp trauma that caused a partial laceration and the second patient had a blunt trauma that caused a dislocation of the flap. The corneas were examined with slitlamp microscopy, computed corneal topography, and confocal microscopy. One flap was repositioned surgically; the other was treated conservatively with an eye patch. The final visual outcomes were good and illustrate the benefit of immediate attention and flap repositioning.

Adult↗

A radialization factor in normal cortical plate restores disorganized radial glia and disrupted migration in a model of cortical dysplasia.

Treatment of pregnant ferrets on embryonic day 24 (E24) with the antimitotic methylazoxy methanol (MAM) leads to a specific constellation of effects in newborn kits, which include a very thin and poorly laminated neocortex, disruption of radial glial cell morphology with early differentiation into astrocytes, and abnormal positioning of Cajal-Retzius cells. We suggest that MAM treatment on E24 results in this model of cortical dysplasia by eliminating a population of cells that produce a factor capable of maintaining radial glia in their normal morphology. The abnormal radial glia, either alone or in combination with other abnormal features, are likely to prevent proper migration into the cortical plate. To test the possibility that normal cortex can provide the missing substance that influences radial glia, slices of E24 MAM-treated cortex were removed at postnatal day 0 (P0) and cultured adjacent to explants of P0 normal cortical plate. By labelling a small number of cells with injections of fluorescent dextrans into the cultured slices, we found that abnormal radial glia in MAM treated slices cocultured adjacent to normal cortical plate were restored toward normal, in comparison to E24 MAM treated slices cultured alone and in other control conditions. We also found that abnormally positioned Cajal-Retzius cells move into the marginal zone and that neurons are able to migrate into the cortical plate more effectively in the coculture condition. These data indicate that normal cortical plate of ferrets contains a factor causing radial glia to maintain their elongated morphology; the improved position of radial glia encourages repositioning of Cajal-Retzius cells and improved neuronal migration into the cortical plate.

Abnormalities, Drug-Induced↗

Beclomethasone dipropionate does not affect mucociliary clearance in patients with chronic obstructive lung disease.

Aerosolized steroids may be implicated in the increased incidence of chest infections. To evaluate such a possibility, we utilized a double-blind study to investigate the acute effect of inhaled beclomethasone dipropionate on mucociliary clearance in 10 patients with chronic obstructive lung disease (5 receiving the drug and 5 placebo). Mucociliary clearance was measured by inhalation of a 99mTc-labelled albumin aerosol. The resulting radioactivity was recorded externally by a large-field gamma camera and dedicated computer for 3 consecutive hours without patient repositioning. After 1-hour baseline recording, the subjects inhaled from a commercial pressurized canister either beclomethasone dipropionate (250 micrograms) or vehicle alone. The recording was then continued for 2 more hours. No statistically significant difference was found in clearance rates throughout the entire period of observation between patients receiving beclomethasone and controls. The data suggest that mechanisms other than mucociliary function impairment are responsible for the increased incidence of chest infections which may accompany steroid treatment by the inhalatory route.

Adult↗

[Early complex treatment of fractures of leg bones and peripheral nerve injuries].

A retrospective analysis of results of treatment of 104 patients with fractures of long tubular bones associated with injuries of peripheral nerves has shown complex therapy to be necessary. Main components of this treatment were biogenic stimulators, vitamin B12, spasmolytic and dehydration drugs in combination with electrophoresis with potassium iodide and thermal procedures. Rapid disturbance of conductivity of nerve trunks after trauma should be followed by revision of the given segment of the extremity in order to remove hematoma and make reposition of displaced fragments of the bone, which can provide recovery of the disturbed function of the nerve.

Adult↗

Chronic dorsal column stimulation via percutaneously inserted epidural electrodes. Preliminary results in 31 patients.

31 patients suffering from intractable pain associated with chronic low back syndrome, terminal cancer, and other disorders have been studied after an average 6 months' treatment by electrical stimulation of the spinal cord applied via electrodes inserted through a Tuohy needle into the epidural space. As judged by three different subjective rating methods, epidural stimulation successfully relieved otherwise intractable chronic pain in from 23 to 26 of the 31 patients. Reported improvements in the ability to perform various everyday activities, and elimination of drug usage by many patients, corroborate this finding. The side effects of stimulation, both as reported subjectively and as measured objectively by sensory testing, were not clinically significant. Spontaneous electrode displacements, leading to loss of analgesia and requiring minor surgery for repositioning, were encountered frequently, as were lead wire failures necessitating replacement. The partially implanted, externally powered stimulation system presently in use also suffers from problems of reliability and convenience to the patient.

Electric Stimulation Therapy↗

Activity reversal of Tet repressor caused by single amino acid exchanges.

We explore by extensive mutagenesis regions in the sequence allowing reversal of the allosteric response of Tet repressor. The wild type requires anhydrotetracycline for induction. About 100 mutants are presented, which, in contrast, require the drug for repression. Their mutations are clustered at the interface of the DNA- and inducer-binding domains. This interface consists of a central hydrophobic region surrounded by several hydrogen bonds. While most of the mutants described here contain two to five mutations, we found five positions in this region of TetR, at which single amino acid exchanges lead to activity reversal. They may disrupt the hydrogen-bonding network bordering the domain interface. We assume that the mutations cause a repositioning of the DNA reading head with respect to the effector binding core so that the same conformational change can result in opposite activities.

Amino Acid Sequence↗

Conscious sedation with intermittent midazolam and fentanyl in electrophysiology procedures.

OBJECTIVES: To determine the safety and efficacy of intermittent midazolam and fentanyl conscious sedation for electrophysiology procedures (EP). BACKGROUND: Intermittent midazolam and fentanyl conscious sedation was administered in 700 consecutive cases (175 radiofrequency ablations, 163 EP studies, 261 pacemakers, and 101 implantable cardioverter-defibrillators) for 471 patients (239 males, 51%) mean age 65 +/- 15 years. The mean dose of midazolam was 0.063 mg/kg/hr and fentanyl was 0.591 microgram/kg/hr. METHODS: Cardiac rate and rhythm were monitored continuously, while blood pressure and arterial oxygen saturation were noninvasively assessed every 5 minutes. Drugs were administered in aliquots of 0.5 to 2.0 mg of midazolam and 6.25 to 25 micrograms of fentanyl as determined by clinical condition every 15 to 30 minutes. RESULTS: There were no deaths. In no case was endotracheal intubation required. Mild hypoxemia (SaO2 > 80%, but < 90%) occurred in 17 cases (2.4%) and was easily reversed with verbal stimulation and oropharyngeal repositioning (12 cases, 1.7%), increased F1O2 (3 cases, 0.4%), or intravenous naloxone (2 cases, 0.3%). Reversible hypotension (systolic blood pressure < 90, but > 60 mmHg) occurred in 14 patients (2.0%) and was corrected with intravenous crystalloid bolus or flumazenil (10 cases, 1.4%) or inotrope infusion (4 cases, 0.6%). No patient stay was prolonged due to sedation. Only five patients (0.7%) had any recollection of the procedure, while two (0.3%) were aware of pain. All hypoxemic episodes occurred during the first hour, whereas 43% (6/14) of hypotensive episodes occurred after the first hour. CONCLUSION: Conscious sedation with intermittent midazolam and fentanyl is safe and efficacious for a broad range of EP procedures.

Aged↗

Haemodynamic changes during laparoscopic anterior fundoplication measured by trans-oesophageal Doppler ultrasound.

We investigated the cardiovascular effects of pneumoperitoneum and steep head-up tilt during laparoscopic fundoplication using an intra-oesophageal Doppler ultrasound probe. Repositioning of the probe proved sufficient to maintain the signal throughout the procedure despite the pneumomediastinum. There was a statistically significant increase in mean arterial blood pressure and a fall in stroke distance but not in systemic vascular resistance. Increasing or decreasing the blood pressure with drugs improved stroke distance. The oesophageal Doppler ultrasound proved a satisfactory method for assessing cardiovascular changes during fundoplication.

Adult↗

Repositioning of pupil for visual disability.

The authors have successfully utilised the technique of photocoagulation of iris in 35 cases for improving the visual acuity in cases suffering from ocular leprosy. The photocoagulation was considered to be very useful in cases with corneal scars, highly vascularised adherent leukomas, where keratoplasty stands a poor risk. It has also been recommended for cases with pinpoint pupil not dilating with drugs for diagnostic and prognostic value.

Adult↗

Clinical results with electrophysiologist-implanted cardioverter-defibrillators.

With the advent of nonthoracotomy leads and smaller devices, implantation techniques for implantable cardioverters defibrillators (ICDs) have been simplified. We reviewed the outcome of pectoral ICD implantation by electrophysiologists in 51 consecutive patients, 47 males and 4 females, mean age 60 +/- 12 years, presenting with aborted sudden cardiac death (14) and drug refractory hypotensive ventricular tachycardia (37). Patients were implanted with either the PCD Jewel 7219D (37) or 72197C (14) Medtronic pectoral ICDs. The mean operative time was 98 +/- 31 minutes. There was no operative mortality. Complications occurred in 2 (4%) patients: right ventricular lead dislodgement requiring lead repositioning occurred in 1 patient, and 1 patient treated with anticoagulants, who had received a subcutaneous patch lead, developed a hematoma not requiring surgical reintervention. The mean defibrillation threshold was 18.6 +/- 5.5 J, but was significantly lower for the 7219C (14.1 +/- 5.0 J) compared to the 7219D (20.6 +/- 4.4 J) device, P = 0.0001. A two-lead system consisting of a right ventricular electrode (RVA) and a superior vena caval lead (SVC) was utilized in 29, RVA/SVC-subcutaneous patch in 5 and active can in 17 patients. Patients were discharged after 4.3 +/- 3 days: The procedure time was significantly shorter for the 7219C device (79.7 +/- 18.9 vs 105.2 +/- 32.8 minutes., P = 0.0035). Over the follow-up period of 8 +/- 5 (range 1-20) months, 26% patients received appropriate therapy (95% antitachycardia pacing, 5% shock). Concomitant antiarrhythmic therapy was utilized in 41% of patients. Ninety-eight percent of patients are alive. One patient died of congestive heart failure. Clinical results with electrophysiologist-implanted pectoral ICDs demonstrate low morbidity and no operative mortality in this clinical series and lower DFTs and shorter procedure times may be achieved with 7219C (active can) device.

Anticoagulants↗

Crystal structures of the class D beta-lactamase OXA-13 in the native form and in complex with meropenem.

The therapeutic problems posed by class D beta-lactamases, a family of serine enzymes that hydrolyse beta-lactam antibiotics following an acylation-deacylation mechanism, are increased by the very low level of sensitivity of these enzymes to beta-lactamase inhibitors. To gain structural and mechanistic insights to aid the design of new inhibitors, we have determined the crystal structure of OXA-13 from Pseudomonas aeruginosa in the apo form and in complex with the carbapenem meropenem. The native form consisted of a dimer displaying an overall organisation similar to that found in the closely related enzyme OXA-10. In the acyl-enzyme complex, the positioning of the antibiotic appeared to be ensured mainly by (i) the covalent acyl bond and (ii) a strong salt-bridge involving the carboxylate moiety of the drug. Comparison of the structures of OXA-13 in the apo form and in complex with meropenem revealed an unsuspected flexibility in the region of the essential serine 115 residue, with possible consequences for the catalytic properties of the enzyme. In the apo form, the Ser115 side-chain is oriented outside the active site, whereas the general base Lys70 adopts a conformation that seems to be incompatible with the activation of the catalytic water molecule required for the deacylation step. In the OXA-13:meropenem complex, a 3.5 A movement of the backbone of the 114-116 loop towards the side-chain of Lys70 was observed, which seems to be driven by a displacement of the neighbouring 91-104 loop and which results in the repositioning of the side-chain hydroxyl group of Ser115 toward the catalytic centre. Concomitantly, the side-chain of Lys70 is forced to curve in the direction of the deacylating water molecule, which is then strongly bound and activated by this residue. However, a distance of ca 5 A separates the catalytic water molecule from the acyl carbonyl group of meropenem, a structural feature that accounts for the inhibition of OXA-13 by this drug. Finally, the low level of penicillinase activity revealed by the kinetic analysis of OXA-13 could be related to the specific presence in position 73 of a serine residue located close to the general base Lys70, which results in a decrease of the number of hydrogen-bonding interactions stabilising the catalytic water molecule.

Amino Acid Sequence↗

Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids.

An important component of triple-drug anti-AIDS therapy is 2', 3'-dideoxy-3'-thiacytidine (3TC, lamivudine). Single mutations at residue 184 of the reverse transcriptase (RT) in HIV cause high-level resistance to 3TC and contribute to the failure of anti-AIDS combination therapy. We have determined crystal structures of the 3TC-resistant mutant HIV-1 RT (M184I) in both the presence and absence of a DNA/DNA template-primer. In the absence of a DNA substrate, the wild-type and mutant structures are very similar. However, comparison of crystal structures of M184I mutant and wild-type HIV-1 RT with and without DNA reveals repositioning of the template-primer in the M184I/DNA binary complex and other smaller changes in residues in the dNTP-binding site. On the basis of these structural results, we developed a model that explains the ability of the 3TC-resistant mutant M184I to incorporate dNTPs but not the nucleotide analog 3TCTP. In this model, steric hindrance is expected for NRTIs with beta- or L- ring configurations, as with the enantiomer of 3TC that is used in therapy. Steric conflict between the oxathiolane ring of 3TCTP and the side chain of beta-branched amino acids (Val, Ile, Thr) at position 184 perturbs inhibitor binding, leading to a reduction in incorporation of the analog. The model can also explain the 3TC resistance of analogous hepatitis B polymerase mutants. Repositioning of the template-primer as observed in the binary complex (M184I/DNA) may also occur in the catalytic ternary complex (M184I/DNA/3TCTP) and contribute to 3TC resistance by interfering with the formation of a catalytically competent closed complex.

Allosteric Regulation↗