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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
PubMed2001

The German cystic fibrosis quality assurance project: clinical features in children and adults.

Cystic fibrosis (CF) is a complex disease which requires interdisciplinary care in specialized CF centres. In Germany, 97 paediatric and adult outpatient clinics agreed to report clinical data of their patients to a newly established registry, the Cystic Fibrosis Quality Assurance (CFQA) project. This article characterizes the design of the CFQA and the health status of the patients enrolled by the end of 1997. Data from 4,306 patients reported to the CFQA project were analysed. Nutritional status and lung function of the patients were examined as well as the use of specific therapeutic interventions. Mean age of all 4,182 patients alive by the end of 1997 was 15.7 yrs (maximum, 58 yrs), and 35.8% of patients were > 18.0 yrs of age. One-third of the CF population were treated in the nine largest centres (each caring for > 100 patients). Abnormal nutritional status (weight-for-height >90% of predicted or body mass index < 19.0 kg m2, respectively) was observed in 26.8% of children and adolescents and in 38.3% of adults. Lung function was abnormal (forced expiratory volume in one second < 80% predicted) in the majority of adults (83.9%) and in 42.5% of the younger patients. The mortality rate was 1.4 of 100 patients in 1997. No clear association of clinical status with centre size was observed. The clinical features of patients treated in German cystic fibrosis centres were generally comparable to those reported from other countries, although improvements are certainly warranted. The Cystic Fibrosis Quality Assurance project represents an important tool for future progress in the quality of cystic fibrosis care.

Adolescent↗
PubMed2001

[Bone mineral density in patients with chronic lung diseases].

PURPOSE: We evaluated bone mineral density and phosphorus calcium status in patients with chronic lung diseases. PATIENTS AND METHODS: A prospective study was conducted in 58 patients (43 men and 15 women, mean age 44 years, age range 16-68 years) who were classed in three groups: chronic obstructive diseases (25 patients), cystic fibrosis (19 patients), and other lung diseases (14 patients). Fifteen percent of the patients were receiving corticosteroid therapy. Bone mineral density of the lumbar spin and the femoral neck was measured. RESULTS: Serum calcium, phosphate, creatinine, osteocalcin and parathyroid hormone were normal. The 25-hydroxyvitamin D (normal=9-40 ng/ml) level was in the lower limits of normal (12 ng/ml) and was severely decreased in 12 patients (<7 ng/ml). CONCLUSION: Chronic lung disease can lead to osteoporosis. Corticosteroids, low vitamin D level, sedentary lifestyle, smoking, and in cystic fibrosis nutritional deficiencies, delayed puberty and hypogonadism are risk factors. Bone density must be measured in order to prevent and treat osteoporosis.

Adolescent↗
PubMed2000

Taking stock of gene therapy for cystic fibrosis.

The identification of the cystic fibrosis (CF) gene opened the way for gene therapy. In the ten years since then, proof of principle in vitro and then in animal models in vivo has been followed by numerous clinical studies using both viral and non-viral vectors to transfer normal copies of the gene to the lungs and noses of CF patients. A wealth of data have emerged from these studies, reflecting enormous progress and also helping to focus and define key difficulties that remain unresolved. Gene therapy for CF remains the most promising possibility for curative rather than symptomatic therapy.

Animals↗
PubMed2000

Balance of mass, momentum, and energy in splintering central collisions for 40Ar up to 115 MeV /Nucleon

For central collisions of (17-115)A MeV 40Ar+Cu, Ag, Au, an overall balance is determined for the average mass, energy, and longitudinal momentum. Light charged particles and fragments are separated into forward-focused and isotropic components in the frame of the heaviest fragment. Energy removal by the isotropic component reaches 1-2 GeV. For such high deposition energies, statistical multifragmentation models predict much more extensive nuclear disassembly than is observed.

Journal Article↗
PubMed2000

Tear production after unilateral removal of the main lacrimal gland in squirrel monkeys.

OBJECTIVE: To study the effects of lacrimal gland removal on basal and reflex tear production and on the ocular surface in the squirrel monkey. METHODS: Unilateral main lacrimal gland removal in 6 squirrel monkeys was followed by Schirmer testing, slit-lamp examination with fluorescein, and collection of basal and reflex (stimulated) tears for analysis of tear protein spectra between 0 and 20 kd, as well as histological evaluation. RESULTS: Schirmer test results showed an 80% decrease in basal tears and a 90% decrease in reflex tears during week 1, and a 32.2% and 33.3% decrease, respectively, at week 20 after surgery, compared with the contralateral control side. However, no gross abnormalities or fluorescein staining were seen in 5 of the 6 monkeys, and the conjunctival surfaces remained normal. The main and accessory lacrimal glands appeared to secrete similar types of proteins. No histological changes were seen in corneal, conjunctival, or eyelid tissues 20 weeks after surgery. CONCLUSIONS: Tears from accessory lacrimal glands were sufficient to maintain a stable tear layer on the cornea, suggesting that so-called basal tear flow is made up of fluid from both main and accessory lacrimal glands and that decreased tear production by the main lacrimal gland is not a causative factor in keratoconjunctivitis sicca. CLINICAL RELEVANCE: This study shows that total removal of the main lacrimal gland does not in itself lead to keratoconjunctivitis sicca. However, the nature of neural control of the accessory glands is not yet clear.

Animals↗
PubMed2000

Development of celiac disease-associated antibodies in offspring of parents with type I diabetes.

AIMS/HYPOTHESIS: The aim of this study was to determine the frequency and temporal development of antibodies related to celiac disease in offspring of parents with Type I (insulin-dependent) diabetes mellitus. METHODS: Sera from 913 offspring of parents with Type I diabetes prospectively followed from birth to the age of 8 years were tested for IgG-transglutaminase antibodies (IgG-tTGCAs), endomysial IgA antibodies (EMA) and gliadin antibodies. RESULTS: We found tTGCAs in 32 (3.5%) of the 913 relatives. Prevalence was related to age and reached 6.5% at age 8 years. Endomysial IgA antibodies were detected in 44% of the relatives with tTGCAs and 0.6% of tTGCA negative relatives and were also most prevalent (5 %) in those aged 8 years. Both tTGCAs and EMAs were more frequent in relatives with the HLA DRB1*03 DQA1*0501 DQB1*02 haplotype (7.1% and 7.2%, respectively; p < 0.005). Antigliadin antibodies were common in both tTGCA positive (42%) and negative (23%) relatives, did not show a relation with age and were less prevalent in relatives with HLA DR3 (p < 0.05). There was no association between the presence of antibodies associated with celiac disease and islet autoantibodies in these relatives. Of the relatives 15 (1.6%) had tTGCAs plus EMAs. In two of these, anti-gliadin antibodies were detected before the detection of tTGCAs and EMAs at the age of 9 months whereas none of the remainder had any antibodies associated with celiac disease before age 2 years. In three there were no detectable antigliadin antibodies in any of the samples tested. Celiac disease without clinical symptoms was diagnosed in 9 of 12 by intestinal biopsy. CONCLUSION/INTERPRETATION. A statistically significant proportion of relatives of patients with Type I diabetes have celiac disease-associated autoimmunity and the silent form of celiac disease early in life. These relatives should, therefore, be considered for celiac antibody screening.

Autoantibodies↗
PubMed2000

A clinical evaluation of a locking orthodontic facebow.

Standard orthodontic facebows may accidentally detach from the appliance buccal tubes at night; this could reduce the effectiveness of extra oral traction and occasionally cause an injury. To try and prevent facebow detachment at night a facebow with a locking mechanism was introduced. This study assessed the ability of 706 consecutively treated patients to learn to wear and use this facebow. The facebows were fitted in 9 different practices supervised by 12 orthodontists. Data from the patients and orthodontists were collected over a 2-year period and covered approximately 166,550 nights. All the orthodontists were able to fit and adjust the facebow; a total of 697 patients successfully used the facebow. Accidental detachment of the facebow at night was reported to be less than 1%. This indicates a significant improvement in the safety of the facebow and should help to improve compliance by increasing the number of hours of wear achieved by the patients.

Accident Prevention↗
PubMed2000

Pretreatment with cationic lipid-mediated transfer of the Na+K+-ATPase pump in a mouse model in vivo augments resolution of high permeability pulmonary oedema.

Resolution of pulmonary oedema is mediated by active absorption of liquid across the alveolar epithelium. A key component of this process is the sodium-potassium ATPase (Na+K+-ATPase) enzyme located on the basolateral surface of epithelial cells and up-regulated during oedema resolution. We hypothesised that lung liquid clearance could be further up-regulated by lipid-mediated transfer and expression of exogenous Na+K+-ATPase cDNA. We demonstrate proof of this principle in a model of high permeability pulmonary oedema induced by intraperitoneal injection of thiourea (2.5 mg/kg) in C57/BL6 mice. Pretreatment of mice (24 h before thiourea) by nasal sniffing of cationic liposome (lipid #67)-DNA complexes encoding the alpha and beta subunits of Na+K+-ATPase (160 microg per mouse), significantly (P<0.01) decreased the wet:dry weight ratios measured 2 h after thiourea injection compared with control animals, pretreated with an equivalent dose of an irrelevant gene. Whole lung Na+K+-ATPase activity was significantly (P<0.05) increased in mice pretreated with Na+K+-ATPase cDNA compared both with untreated control animals as well as animals pretreated with the irrelevant gene. Nested RT-PCR on whole lung homogenates confirmed gene transfer by detection of vector-specific mRNA in three of four mice studied 24 h after gene transfer. This demonstration of a significant reduction in pulmonary oedema following in vivo gene transfer raises the possibility of gene therapy as a novel, localised approach for pulmonary oedema in clinical settings such as ARDS and lung transplantation.

Animals↗
PubMed2000

Molecular epidemiology of community-acquired Staphylococcus aureus in families with and without cystic fibrosis patients.

The molecular epidemiology of Staphylococcus aureus nasal commensal strains and community-acquired infecting strains was assessed by comparison of prevalence, persistence, transmission rate, and clonal distribution of S. aureus in families with and without cystic fibrosis (CF) patients. Isolates were typed by pulsed-field gel electrophoresis. CF patients without antibiotic treatment had a significantly higher nasal prevalence (66%) of S. aureus than did treated patients (29%; P<.001) or healthy controls (32%; P<.001), suggesting that persons with CF have a higher susceptibility to this organism. Strain transmission was frequent within both CF (55%) and non-CF (62%) families. After 3 and 19 months, 57% and 21%, respectively, of all persons still harbored the same S. aureus strain. Most of the isolates (78%) belonged to 8 of 38 genome types common in CF patients and in healthy persons. The predominant occurrence of a limited number of S. aureus clones within the community suggests evolutionary mechanisms for the selection of certain strains without an obvious association with disease.

Community-Acquired Infections↗
PubMed2000

Update in Sjögren syndrome.

Sjögren syndrome (SS), the second most common autoimmune rheumatic disease, refers to keratoconjunctivitis sicca and xerostomia resulting from immune lymphocytes that infiltrate the lacrimal and salivary glands. However, differential diagnosis remains confusing due to the high prevalence of vague symptoms of dryness, fatigue, and myalgias in the general population. The problems of diagnosis are further compounded by the finding of "positive" antinuclear antibodies in a high percent of the general population. Unless minor salivary gland biopsies are read by experienced observers, nonspecific changes of sialadenitis are frequently confused with the focal lymphocytic infiltrates that are characteristic of SS. The distinction between fibromyalgia patients with low titer antinuclear antibodies and primary SS remains difficult. Even in patients fulfilling strict criteria for SS, the genomic search for critical genes has proven difficult due to the multigenic pattern of inheritance and strong role of currently undefined environmental factors. No single environmental factor has been detected in the majority of SS patients. SS-like syndrome has been detected in certain patients with HTLV-1 and hepatitis C infection, providing clues to pathogenesis. Even in SS patients with marked sicca symptoms, minor salivary gland biopsy shows that almost 50% of glandular cells are still detected on biopsy. These results imply the importance of immune factors such as cytokines and autoantibodies in decreasing neuro-secretory circuits and induction of glandular dysfunction. Of potential importance, an antibody against muscarinic M3 receptor that can decrease secretory function when injected into rodents is frequently found in the sera of SS patients. Newly developed topical and oral therapies can ease the oral and ocular dryness. Orally administered agonists of the muscarinic M3 receptor (pilocarpine and cevimeline) have recently been approved by the US Food and Drug Administration to increase salivary secretion. Topical ocular use of low-dose corticosteroids or cyclosporin may decrease conjunctival surface inflammation. In a Phase II double-blind study, orally administered interferon alpha (150 U) led to improved saliva flow and symptoms. In pregnant patients with evidence of fetal distress, oral dexamethasone is preferred because this agent crosses the placenta effectively. In animal models, antagonists of tumor necrosis factor and inhibitors of de novo pyrimidine synthesis appear promising.

Adult↗
PubMed2000

Interleukin-6 levels in the conjunctival epithelium of patients with dry eye disease treated with cyclosporine ophthalmic emulsion.

PURPOSE: To evaluate interleukin-6 (IL-6) levels in the conjunctival epithelium of patients with moderate to severe dry eye disease before and after treatment with cyclosporin A ophthalmic emulsion (CsA) or its vehicle. METHODS: Conjunctival cytology specimens were obtained from a subset of patients enrolled in a 6-month randomized, double-masked clinical trial of the efficacy and safety of topical CsA at baseline and after 3 and 6 months of B.I.D. treatment with 0.05% cyclosporine emulsion (n = 13), 0.1% cyclosporine emulsion (n = 8), or vehicle (n = 10). RNA was extracted and a competitive reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the levels of mRNA encoding the inflammatory cytokine IL-6 and a housekeeping gene, G3PDH. Levels of IL-6 and G3PDH were measured and compared. RESULTS: There was no change from baseline in the level of G3PDH after 3 or 6 months in any group. IL-6 normalized for G3PDH (IL-6/G3PDH ratio) was not different from baseline at 3 months but showed a significant decrease from baseline in the group treated with 0.05% CsA (p = 0.048) at 6 months. No significant between-group differences were noted and no correlation was observed between the change in IL-6/G3PDH and corneal fluorescein staining. CONCLUSIONS: This preliminary, small-cohort study showed a decrease in IL-6 in the conjunctival epithelium of moderate to severe dry eye patients treated with 0.05% CsA for 6 months. The observed decrease suggests that dry eye disease involves immune-mediated inflammatory processes that may be decreased by treatment with topical ophthalmic cyclosporine.

Administration, Topical↗
PubMed2000

Comparative evaluation of serologic tests for celiac disease: a European initiative toward standardization.

BACKGROUND: Serologic methods have been used widely to test for celiac disease and have gained importance in diagnostic definition and in new epidemiologic findings. However, there is no standardization, and there are no reference protocols and materials. METHODS: The European working group on Serological Screening for Celiac Disease has defined robust noncommercial test protocols for immunoglobulin (Ig)G and IgA gliadin antibodies and for IgA autoantibodies against endomysium and tissue transglutaminase. Standard curves were linear in the decisive range, and intra-assay variation coefficients were less than 5% to 10%. Calibration was performed with a group reference serum. Joint cutoff limits were used. Seven laboratories took part in the final collaborative study on 252 randomized sera classified by histology (103 pediatric and adult patients with active celiac disease, 89 disease control subjects, and 60 blood donors). RESULTS: IgA autoantibodies against endomysium and tissue transglutaminase rendered superior sensitivity (90% and 93%, respectively) and specificity (99% and 95%, respectively) over IgA and IgG gliadin antibodies. Tissue transglutaminase antibody testing showed superior receiver operating characteristic performance compared with gliadin antibodies. The K values for interlaboratory reproducibility showed superiority for IgA endomysium (0.93) in comparison with tissue transglutaminase antibodies (0.83) and gliadin antibodies (0.82 for IgG, 0.62 for IgA). CONCLUSIONS: Basic criteria of standardization and quality assessment must be fulfilled by any given test protocol proposed for serologic investigation of celiac disease. The working group has produced robust test protocols and reference materials available for standardization to further improve reliability of serologic testing for celiac disease.

Adolescent↗
PubMed2000

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↗
PubMed2000

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↗