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Biomedical subjects

M Stern

Publications and source records attributed to M Stern.

At least 55 records · Page 3Linked to original sources

Reduced frequency of retention wire fractures suggests that elective explantation of affected atrial leads is no longer indicated.

Since 1994, 611 patients with atrial Accufix leads have been followed. Consideration was given to explanting these leads based on the presence or absence of fractures of the retention wire. All leads were followed according to a protocol proposed by the manufacturer, chiefly by regular 6-month high quality X rays and fluoroscopic evaluation. The impact of various conditions on the incidence of fracture was evaluated, such as the shape and location of the lead, prior open heart surgery, and the implantation route. The only factor related to the frequency of fractures was the shape of the lead, fractures occurring statistically more frequently if the leads were pulled from their normal J shape into an L or straightened configuration. The frequency of fractures has plateaued at 6 through 9 years with no further occurrence of Class III or IV fractures (protrusion of the fractured segment). Altogether there were nine (1.5%) Class III and Class IV fractures at the 9-year follow-up. Actuarial survival, in Class I or II, was 97%. We concluded, that the frequency of retention wire fractures has plateaued. This information coupled with the knowledge that the Accufix lead extraction can be difficult and dangerous, suggests that the remaining leads are best left in place.

Adolescent↗

Insulinlike growth factor-1 in lung transplants with obliterative bronchiolitis.

Bronchiolitis obliterans syndrome (BOS) is the major complication limiting survival of lung transplant recipients (Tx patients). The mechanisms underlying this fibrotic process are not known. We assessed IGF-1 and IGFBP-3 expression, critical mediators in different models of pulmonary fibrosis, in nine Tx patients. Three of them developed a BOS at 8, 14, and 17 mo postgraft, respectively. Two of the remaining six displayed a recurrent cytomegalovirus (CMV) infection, and four are in stable condition. IGF-1 mRNA expression was quantitated by RT-PCR in cells from four to six BAL per patient performed during the first 6 mo postgraft. Contrasting with a constantly low expression of IGF-1 mRNA in BAL cells from the six patients without BOS, the three patients with BOS presented marked peaks of IGF-1 on two to five occasions during the study period. These peaks, 3- to 13-fold increased compared with values from the former patients, preceded the diagnosis of BOS by 7, 13, and 17 mo, respectively. On the other hand, IGFBP-3 was highly and exclusively expressed in the three patients with BOS, the mRNA as well as the gene product as demonstrated by Western blotting. Our data strongly argue for a role of IGF-1 and IGFBP-3 in the fibrotic process underlying BOS, and for their possible value as an early marker of this complication.

Biopsy↗

Long-term deep brain stimulation in a patient with essential tremor: clinical response and postmortem correlation with stimulator termination sites in ventral thalamus. Case report.

Essential tremor can be suppressed with chronic, bilateral deep brain stimulation (DBS) of the ventralis intermedius nucleus (Vim), the cerebellar receiving area of the motor thalamus. The goal in this study was to correlate the location of the electrodes with the clinical efficacy of DBS in a patient with essential tremor. The authors report on a woman with essential tremor in whom chronic bilateral DBS directed to the ventral thalamus produced adequate tremor suppression until her death from unrelated causes 16 months after placement of the electrodes. Neuropathological postmortem studies of the brain in this patient demonstrated that both stimulators terminated in the Vim region of the thalamus, and that chronic DBS elicited minor reactive changes confined to the immediate vicinity of the electrode tracks. Although the authors could not identify neuropathological abnormalities specific to essential tremor, they believe that suppression of essential tremor by chronic DBS correlates with bilateral termination of the stimulators in the Vim region of the thalamus.

Brain Mapping↗

Intestinal ultrasonography in children and young adults: bowel wall thickness is age dependent.

The purpose of this study was to investigate bowel wall thickness in children, adolescents, and young adults as measured by ultrasonography. Ultrasonographic evaluation of the small bowel and the colon was performed in 128 subjects (age range, 3 days to 40 years). Bowel wall thickness increased significantly (P < 0.0001) increased with age, reaching a maximum colon wall thickness of 2.0 mm at the age range of 20 to 29 years. In the ileum, maximum wall thickness reached 1.5 mm at the age range of 10 to 14 years. The findings emphasize the need for age-specific normal values for bowel wall thickness measured by ultrasonography.

Adolescent↗

[Specific aspects and care of lung involvement in adults with cystic fibrosis].

Respiratory impairment is present in almost all adult cystic fibrosis patients and makes the prognosis. Viscous, infected and abundant secretions, inflammation and bronchial oedema, bronchoconstriction and respiratory muscle fatigue lead to airway obstruction, bronchiectasis and respiratory failure. The disease is preferentially located in the upper lobes. Exacerbations of the disease are due to bronchial infections and are often responsible for drops of the respiratory function. Regular spirometric surveillance is fundamental for the prognosis and the assessment of the effects of the treatment. Among adult patients chronic colonisation with mucoid and often multiresistant strains of Pseudomonas Aeruginosa are common. It is treated with i.v. high doses antibiotic courses and nebulized antibiotics between i.v. courses. Respiratory failure may require long term oxygen and non invasive mechanical ventilation. Systemic hypervascularization around the bronchiectasis may lead to moderate to severe hemoptysis, which may require embolization. Pneumothorax are associated with poor prognosis and are treated by pleural drainage and if failure by thoracoscopy.

Adrenal Cortex Hormones↗

[Lung transplantation in cystic fibrosis in adults. Patient selection criteria].

Lung transplantation (LT) became during the ten past years an important therapeutic option for cystic fibrosis adult patients with end-stage chronic lung disease. LT clearly improves both survival and long term quality of life. A rigorous selection of the candidates is of paramount importance to improve the results of LT because of the lack of shortage of organs. This selection requires a multidisciplinary assessment to refuse patients with absolute exclusion criteria or general medical conditions that impact negatively on short- and long-term outcome. One of the major difficulties is to determine the best time to refer patients to transplantation, arguing the comparison between the predicted survival time of the candidate, under optimal medical therapy, with or without LT. The selection period is also an active process to prepare the patients to the postoperative follow-up and includes a nutritional and rehabilitation program with an educational and psychological preparation. The aim of the present work is to gather the worldwide principles of the selection of the CF patients for LT, commonly used by the LT centers. These recommendations should provide the CF center practitioners with the main elements to prepare their patients to an LT project before a relentless end-stage clinical condition.

Adolescent↗

Pulmonary giant bulla in Wegener's granulomatosis.

The association of lung emphysema with severe systemic antineutrophil cytoplasm antibodies (ANCA)-positive vasculitis, such as Wegener's granulomatosis is unusual since only four cases have been described previously. We report the first case of a 30 year-old smoker man presenting with biopsy-proven Wegener's granulomatosis, who developed a bullous emphysema during severe active lung vasculitis, in association with positive ANCA disclosing an anti-myeloperoxydase pattern. Alpha 1-antitrypsin deficiency, a known risk factor of lung emphysema recently found to be associated with anti-proteinase 3-positive vasculitis, was not present in this patient. Cigarette smoking, in association with severe lung vasculitis, might have contributed to the development of this emphysematous lesion.

Adult↗

Nebulized cyclosporine in the rat: assessment of regional lung and extrapulmonary deposition.

BACKGROUND: Nebulized cyclosporine (CsA) has been shown to limit lung allograft rejection as well as intramuscular (IM) CsA, with limited blood diffusion. The present study determined the pharmacokinetic parameters of nebulized CsA, by the assessment of regional lung deposition and extrapulmonary diffusion of CsA. METHODS: CsA was given either by IM injection (10 mg/kg) or by aerosol (at 10 and 25 mg/kg doses); 70 rats were killed at 25 and 50 min, and at 2, 4, 6, 8, 12, 24, or 48 hr after CsA administration. CsA levels were measured in the whole lung, in central and peripheral parts of the lung, in whole blood, kidney, and heart. The areas under the concentration time curves (AUCs) were determined. RESULTS: In blood, kidney, and heart, CsA levels were significantly higher for IM than for aerosol administrations at 10 and 25 mg/kg doses. In the whole lung, the AUC was greater for the aerosol route at 25 mg/kg doses (588 ng x hr/mg) than for the low-dose (200 ng x hr/mg) or IM administration (200 ng x hr/mg). The central to peripheral index of CsA (ratio of AUC central/peripheral part of the lung) was not significantly different for both aerosol administrations (0.63 and 0.69, respectively) and for the IM route (0.81). CONCLUSIONS: Nebulized CsA allows better pulmonary concentration than IM administration, with equivalent central and peripheral deposition whatever the mode of administration, and results in lower levels in blood, kidney, and heart.

Administration, Intranasal↗

Octopamine in the locust brain: cellular distribution and functional significance in an arousal mechanism.

This review summarizes the distribution of octopamine-like immunoreactive neurons in the brain of the locust and the functional significance of a subset of them in an arousal mechanism in the visual system. A small set of identifiable octopamine-immunoreactive neurons lies in the ventromedial brain. Their cell bodies are large and readily accessible, which allows their removal and analysis of their biogenic amine content using gas-chromatography mass-spectrometry to confirm that they are genuinely octopaminergic. The neurons project from the central brain to the optic lobes where they arborize extensively in the medulla and lobula. There they release octopamine in response to multimodal input in the central brain. This evokes dishabitution in the locust's movement-detection system, suggesting an arousal mechanism.

Animals↗

Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial.

BACKGROUND: We and others have previously reported significant changes in chloride transport after cationic-lipid-mediated transfer of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to the nasal epithelium of patients with cystic fibrosis. We studied the safety and efficacy of this gene transfer to the lungs and nose of patients with cystic fibrosis in a double-blind placebo-controlled trial. METHODS: Eight patients with cystic fibrosis were randomly assigned DNA-lipid complex (active) by nebulisation into the lungs followed 1 week later by administration to the nose. Eight control patients followed the same protocol but with the lipid alone (placebo). Safety was assessed clinically, by radiography, by pulmonary function, by induced sputum, and by histological analysis. Efficacy was assessed by analysis of vector-specific CFTR DNA and mRNA, in-vivo potential difference, epifluorescence assay of chloride efflux, and bacterial adherence. FINDINGS: Seven of the eight patients receiving the active complex reported mild influenza-like symptoms that resolved within 36 h. Six of eight patients in both the active and placebo groups reported mild airway symptoms over a period of 12 h following pulmonary administration. No specific treatment was required for either event. Pulmonary administration resulted in a significant (p<0.05) degree of correction of the chloride abnormality in the patients receiving active treatment but not in those on placebo when assessed by in-vivo potential difference and chloride efflux. Bacterial adherence was also reduced. We detected no alterations in the sodium transport abnormality. A similar pattern occurred following nasal administration. INTERPRETATION: Cationic-lipid-mediated CFTR gene transfer can significantly influence the underlying chloride defect in the lungs of patients with cystic fibrosis.

Adult↗

Unitary Ca2+ current through cardiac ryanodine receptor channels under quasi-physiological ionic conditions.

Single canine cardiac ryanodine receptor channels were incorporated into planar lipid bilayers. Single-channel currents were sampled at 1-5 kHz and filtered at 0.2-1.0 kHz. Channel incorporations were obtained in symmetrical solutions (20 mM HEPES-Tris, pH 7.4, and pCa 5). Unitary Ca2+ currents were monitored when 2-30 mM Ca2+ was added to the lumenal side of the channel. The relationship between the amplitude of unitary Ca2+ current (at 0 mV holding potential) and lumenal [Ca2+] was hyperbolic and saturated at approximately 4 pA. This relationship was then defined in the presence of different symmetrical CsCH3SO3 concentrations (5, 50, and 150 mM). Under these conditions, unitary current amplitude was 1.2 +/- 0.1, 0.65 +/- 0.1, and 0.35 +/- 0.1 pA in 2 mM lumenal Ca2+; and 3.3 +/- 0.4, 2.4 +/- 0. 2, and 1.63 +/- 0.2 pA in 10 mM lumenal Ca2+ (n > 6). Unitary Ca2+ current was also defined in the presence of symmetrical [Mg2+] (1 mM) and low [Cs+] (5 mM). Under these conditions, unitary Ca2+ current in 2 and 10 mM lumenal Ca2+ was 0.66 +/- 0.1 and 1.52 +/- 0.06 pA, respectively. In the presence of higher symmetrical [Cs+] (50 mM), Mg2+ (1 mM), and lumenal [Ca2+] (10 mM), unitary Ca2+ current exhibited an amplitude of 0.9 +/- 0.2 pA (n = 3). This result indicates that the actions of Cs+ and Mg2+ on unitary Ca2+ current were additive. These data demonstrate that physiological levels of monovalent cation and Mg2+ effectively compete with Ca2+ as charge carrier in cardiac ryanodine receptor channels. If lumenal free Ca2+ is 2 mM, then our results indicate that unitary Ca2+ current under physiological conditions should be <0.6 pA.

Algorithms↗

How do current Senior Registrar job profiles relate to proposed Specialist Registrar FTTA posts? Fixed-term training appointments.

The proposed United Kingdom training pathway for Orthodontic Specialist Registrars is now accepted to be of 3 years duration. In the final year, Specialist Registrars will take the Membership in Orthodontics, with the end point of training marked by the award of the Certificate of Completion on Specialist Training (CCST). There will be a predetermined number of fixed-term training appointments (FTTAs), available through competitive entry, which will provide 2 years of additional training and lead to eligibility to apply for a Consultant appointment. The end point of the Specialist Registrar (FTTA) will be marked by the Intercollegiate Specialty Examination (ISE). The current 3-year Senior Registrar orthodontic training will be reduced to 2 years as the transition to the Specialist Registrar FTTA grade occurs. In the light of these changes, a survey of full time NHS Senior Registrar posts was carried out to examine current job profiles with particular reference to their suitability for assimilation into the Specialist Registrar (FTTA) grade and preparation for the ISE.

Diagnosis-Related Groups↗

Targeting for thalamic deep brain stimulator implantation without computer guidance: assessment of targeting accuracy.

The authors assess the accuracy of targeting nucleus ventralis intermedius (Vim) with fast spin echo inversion recovery (FSE/IR) magnetic resonance imaging (MRI) in 18 successful deep brain stimulator (DBS) implants for medically refractory tremor. FSE/IR-MRI-derived coordinates are compared to the final coordinates employed for DBS lead placement, selected with intraoperative neurophysiology. The authors conclude that FSE/IR MRI is sufficiently reliable to serve as the sole means of anatomically targeting Vim for DBS lead placement. An independent computer workstation is not required for accurate targeting; however, intraoperative neurophysiology remains essential.

Brain Mapping↗

Enhanced peptide-binding capacities of small intestinal brush border membranes in celiac disease.

In pathogenesis of celiac disease, the significance of prolamin peptide interactions with enterocytes is controversial. Changes in cellular metabolism induced by gliadin peptides, as well as uptake and presentation by enterocytes, are discussed. We analyzed peptide binding to enterocytic membranes as a potential key event. Binding capacities of brush border membranes isolated from small intestinal biopsies of untreated (n = 49) and treated celiac patients on a gluten-free diet (n = 30), as well as control subjects (n = 43), were measured with a dot blot chemiluminescence assay. Synthetic gliadin peptides comprising amino acid position 8-19 (G XIV) and 30-41 (G XI) of alpha-gliadins, a peptic-tryptic digest of gliadin (PT-GLI), and a synthetic zein peptide were used. Comparing treated celiac patients with controls, we observed significantly enhanced membrane-binding of PT-GLI [mean 122.4 densitometric units/microg (95% confidence interval 116.0-128.9) vs 108.9 (102.1-115.7)] and of zein peptide [50.2 (38.4-61.9) vs 28.8 (13.4-44.2)], but only slightly increased binding of the synthetic gliadin peptides G XIV [65.5 (60.6-70.5) vs 62.4 (56.3-68.5) and G XI [75.2 (69.8-80.6) vs 65.9 (55.2-76.5)]. Independent of patient group, membrane-binding capacities for celiac-active gliadin peptides exceeded those of the zein peptide. Thus, interaction of gliadin peptides with the apical enterocytic membrane was not found exclusively in celiac disease. Furthermore, increased binding capacities in treated celiac disease were not confined to celiac-active peptides. Quantitative differences in gliadin peptide binding as a primary characteristic in celiac disease might contribute to pathogenetic effects exerted on small intestinal epithelial cells.

Adolescent↗