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Biomedical subjects

T Lerner

Publications and source records attributed to T Lerner.

At least 19 recordsLinked to original sources
PubMed2006

[Lumbar spinal stenosis].

Lumbal spinal stenosis is gaining more and more clinical relevance because of changing population structure and increasing demand on lifequality in the elderly. Current treatment recommendations are based on clinical experience, expert opinions and single studies rather than on proven evidence. The radiologic degree of stenosis does not correlate with the patients' clinical situation. It is not the main factor indicating surgery but rather the typical history and spinal claudication. Symptomatic patients with light to moderate complaints should undergo multimodal conservative treatment. Epidural injections, delordosating physiotherapy and medication are useful. In patients with severe symptomatic stenosis surgery is indicated after a conservative treatment of 3 months. Relevant pareses or a cauda equina syndrome are absolute indications for surgery. The general aim is to decompress sufficiently while maintaining or restoring segmental stability. A laminectomy is not necessarily required. In patients with accompanying degenerative Meyerding grade I-II spondylolisthesis or instability in functional radiographs, fusion or dynamic stabilisation are recommended in addition to decompression, depending on the patient's age and activity level.

Decompression↗
PubMed2005

[Lumbar disc arthroplasty. Established technique or experimental procedure?].

Lumbar interbody fusion used to be the most common surgical treatment for painful lumbar disc degeneration. With the technical development of total disc prostheses, replacement of the degenerated disc by a motion preserving implant has become a widely discussed alternative. The advantages of such replacement appear to include the prevention of adjacent segment disease as well as less perioperative morbidity. Three types of total disc prostheses are currently in common use. Although numerous studies have been made, a review of the literature reveals only two multicenter randomized studies comparing the outcome of disc prostheses with a control group of fusion patients. After 2 years, the available results show similar improvement after both types of surgery without significant differences. However, there is a trend towards faster recovery and improvement in disc arthroplasty patients. The long-term results of current and future randomized studies, including studies comparing results after disc arthroplasty, with results of standardized conservative therapies will determine the fate of lumbar disc prostheses.

Adolescent↗
PubMed2003

Titanium cages in the surgical treatment of severe vertebral osteomyelitis.

The role of spinal implants in the presence of infection is critically discussed. In this study 20 patients with destructive vertebral osteomyelitis were surgically treated with one-stage posterior instrumentation and fusion and anterior debridement, decompression and anterior column reconstruction using an expandable titanium cage filled with morsellised autologous bone graft. The patients' records and radiographs were retrospectively analysed and follow-up clinical and radiographic data obtained. At a mean follow-up of 23 months (range 12-56 months) all cages were radiographically fused and all infections eradicated. There were no cases of cage dislocation, migration or subsidence. Local kyphosis was corrected from 9.2 degrees (range -20 degrees to 64 degrees ) by 9.4 degrees to -0.2 degrees (range -32 degrees to 40 degrees ) postoperatively and lost 0.9 degrees during follow-up. All five patients with preoperative neurological deficits improved to Frankel score D or E. Patient-perceived disability caused by back pain averaged 7.9 (range 0-22) in the Roland-Morris score at follow-up. In cases of vertebral osteomyelitis with severe anterior column destruction the use of titanium cages in combination with posterior instrumentation is effective and safe and offers a good alternative to structural bone grafts. Further follow-up is necessary to confirm these early results.

Aged↗
PubMed1999

Progress toward the cloning of CLN6, the gene underlying a variant LINCL.

Marked clinical heterogeneity is seen in the late-infantile subtype of NCL (LINCL), complicating genetic analysis. In addition to the classical subtype, encoded by CLN2 on chromosome 11p15.5, several variant subtypes have also been described. In this paper, we report our progress in cloning a variant LINCL gene mapped in a small group of Costa Rican families. Clinically, these patients appear similar to classical LINCL patients, except onset of the disease is delayed and the course is milder. Extended haplotype analysis confirms the localization of this gene to chromosome 15q21-22, where CLN6 has also been mapped. Using now-standard positional cloning techniques, we have developed a physical map of our candidate region. These clones have been used to order genetic markers, STSs, and ESTs in this region and will be used for the identification of the disease gene transcript.

Chromosomes, Artificial, Yeast↗
PubMed1997

Effects of angiotensin II receptor blockade on hypoxia-induced right ventricular hypertrophy in rats.

It was the aim of the present study to characterize the hemodynamic, biochemical and morphologic effect of angiotensin II receptor blockade on hypoxia-induced right ventricular hypertrophy in rats. Isolated right ventricular hypertrophy was induced in female Sprague-Dawley rats by intermittent hypoxia (IH; 10% O2, 8 h/day, 5 days/week, 20 days of exposition, n=15). After completion of IH, left- (LV) and right-ventricular (RV) hemodynamic parameters were measured under room air conditions in the intact, thiopental-anesthetized animals with special Millar ultraminiature tipcatheter-manometers. Cardiac output was determined using the thermodilution method. Cell volume (CV) of isolated cardiomyocytes was measured with a Coulter Channellyzer after collagenase cell isolation. The specific activities of the myocardial pentose phosphate pathway enzymes glucose-6-phosphate-dehydrogenase (G-6-PD) and 6-phosphogluconate-dehydrogenase (6-PGD) were determined using a spectrophotometric assay. IH caused a rise in right ventricular systolic pressure (RVSP) from 38.1+/-0.83 to 58.1+/-1.42 mmHg and an increase in the RV weight/body weight ratio (RVW/BW) from 0.884+/-0. 053 to 1.166+/-0.049 mg/g. The activities of G-6-PD and 6-PGD were significantly increased after IH in the RV, but not in the LV. CV was increased from 24 248+/-1193 to 29 541+/-1765 micrometer 3, myocardial cell length was unchanged. IH had no influence on the LV parameters or cardiac output. Co-infusion of the angiotensin II receptor antagonist losartan (LO; 12 mg/kg/d i.p., n=14) during the IH period reduced the rises in RVSP (49.4+/-2.06 mmHg), RVW/BW (0. 99+/-0.072 mg/g), G-6-PD and 6-PGD significantly, but not completely. The increase in CV, however, was prevented (24 524+/-2370 micrometer 3) entirely. We conclude from these data that the IH-induced RV-hypertrophy was primarily of the concentric type. LO attenuated the hypoxia-induced isolated RV hypertrophy and significantly reduced the metabolic response of the RV. The LO effect was most potent with regard to the increase in cardiomyocyte volume.

Angiotensin Receptor Antagonists↗
PubMed1995

Peripherin gene is linked to keratin 18 gene on human chromosome 12.

Peripherin is a neuron-specific intermediate filament (IF) protein, found primarily in phylogenetically old regions of the nervous system. Whereas other neuronal IF genes have only two to three introns and are scattered in the genome, the peripherin gene (PRPH) has a complex intron-exon structure like nonneuronal IF genes that are clustered in tandem arrays, e.g., those encoding the keratins. We used a cosmid containing the human peripherin gene (PRPH) to determine its chromosomal location in relationship to nonneuronal IF genes. Using a rodent-human mapping panel, we localized the PRPH gene to human chromosome 12. Since a cluster of keratin genes maps to 12q12-13, polymorphic markers were developed for PRPH and for one of the keratin genes presumed to be in the cluster, keratin 18 (KRT18). Both markers were typed in CEPH reference families. Pairwise and multipoint analyses of the CEPH data revealed that KRT18 is tightly linked to DNA markers D12S4, D12S22, D12S90, D12S96 and D12S103, which lie between D12S18 and D12S8, with odds greater than 1000:1. These markers are physically located at 12q11-13, thus supporting the fine localization of KRT18 in or near the group of type II keratins in this region. Furthermore, linkage analysis showed that the peripherin gene (PRPH) is tightly linked to KRT18 (Z = 15.73, theta = 0.013), and therefore appears to be in close proximity to the cluster.

Base Sequence↗
PubMed1993

Characterization of a duplication in the terminal band of 4p by molecular cytogenetics.

An infant with multiple anomalies including small head, large apparently low-set ears, beaked nose, micrognathia, choanal stenosis, proptosis, atrial-septal defect, and left inguinal hernia was found, on chromosome analysis, to have a longer than normal terminal band 4p16 by G and R-banding. In situ hybridization of biotin-labeled DNA probes C39, BJ14, BJ54, BJ19, BJ7, and BJ11 showed them to be duplicated. Probes I14, A157.1, and the telomeric sequence, (TTAGGG)n, which hybridized to the more distal part of 4p16.3, were not duplicated. These results confirm the impression by G and R-banding of a duplication within band 4p16, a region extending from approximately 2.1 Mb from the telomere, proximally, to the junction of 4p16.1 and 4p15.3. This is the smallest confirmed duplication of distal 4p reported to date, with many of the classical findings of dup(4p) syndrome.

Abnormalities, Multiple↗
PubMed1993

Localization of juvenile, but not late-infantile, neuronal ceroid lipofuscinosis on chromosome 16.

The neuronal ceroid lipofuscinoses (NCL) are a group of progressive neurodegenerative disorders characterized by the deposition of autofluorescent proteinaceous fingerprint or curvilinear bodies. We have found that CLN3, the gene underlying the juvenile form of NCL, is very tightly linked to the dinucleotide repeat marker D16S285 on chromosome 16. Integration of D16S285 into the genetic map of chromosome 16 by using the Centre d'Etude du Polymorphisme Humain panel of reference pedigrees yielded a favored marker order in the CLN3 region of qtel-D16S150-.08-D16S285-.04-D16S148-.02-D16S 67-ptel. The most likely location of the disease gene, near D16S285 in the D16S150-D16S148 interval, was favored by odds of greater than 10(4):1 over the adjacent D16S148-D16S67 interval, which was recently reported as the minimum candidate region. Analysis of D16S285 in pedigrees with late-infantile NCL virtually excluded the CLN3 region, suggesting that these two forms of NCL are genetically distinct.

Adolescent↗
PubMed1992

Molecular analysis of human chromosome 16 cosmid clones containing NotI sites.

To test the feasibility of using cloned NotI sites as markers for physical mapping, we have screened for cosmid clones spanning the NotI sites on human Chromosome (Chr) 16. Fluorescence in situ hybridization analysis of these clones confirms the previously reported cluster of NotI sites on 16p13.3. Methylation status of the cloned NotI sites on genomic DNA was established by hybridization of the cosmids to Southern blots containing EcoRI and EcoRI/NotI digest of genomic DNA. These results indicated that four of six clones included in our study can be used as linking clones for physical mapping. Two clones have NotI sites which are not cleavable in the cell lines tested. In one clone, the NotI site exists as an isolated rare-cutting restriction enzyme site, whereas in the other clone the NotI site appears to be island-related.

Blotting, Southern↗
PubMed1992

Rapid detection of chromosome aneuploidies in uncultured amniocytes by using fluorescence in situ hybridization (FISH).

Herein we report the results of the first major prospective study directly comparing aneuploidy detection by fluorescence in situ hybridization of interphase nuclei with the results obtained by cytogenetic analysis. We constructed probes derived from specific subregions of human chromosomes 21, 18, 13, X, and Y that give a single copy-like signal when used in conjunction with suppression hybridization. A total of 526 independent amniotic fluid samples were analyzed in a blind fashion. All five probes were analyzed on 117 samples, while subsets of these five probes were used on the remaining samples (because of insufficient sample size), for a total of over 900 autosomal hybridization reactions and over 400 sex chromosome hybridization reactions. In this blind series, 21 of 21 abnormal samples were correctly identified. The remaining samples were correctly classified as disomic for these five chromosomes. The combination of chromosome-specific probe sets composed primarily of cosmid contigs and optimized hybridization/detection allowed accurate chromosome enumeration in uncultured human amniotic fluid cells, consistent with the results obtained by traditional cytogenetic analysis.

Amniocentesis↗
PubMed1991

The effect of toothbrushing on a hybrid composite resin.

This study observed the effect of various toothpastes on a hybrid composite resin to determine the difference in surface roughness as measured by a profilometer. Slurries (100 gm dentifrice/100 gm H2O) of eight toothpastes were tested by brushing composite resin samples 20,000 times and recording changes in surface smoothness with a profile meter. The surface topography of a hybrid composite resin was altered by routine toothbrushing; the effect of Colgate toothpaste was a statistically smoother surface than found with the other dentifrices; and the surface topography of acrylic resin was altered less by Colgate, Crest, Viadent, and Supersmile than the more abrasive Shane, Sensodyne, Rembrandt, and Topol dentifrices.

Acrylic Resins↗
PubMed1987

Molecular genetic approaches to cystic fibrosis.

Cystic fibrosis (CF) is the most common lethal genetic disease of white populations. The underlying biochemical defect remains unknown, but recently polymorphic DNA markers linked to the cystic fibrosis gene have been discovered. These markers provide useful tools both for antenatal diagnosis and carrier detection, and for isolating the cystic fibrosis gene. In this paper we present data summarizing the results of retrospective and prospective antenatal series as well as a report on molecular approaches to isolation of the cystic fibrosis gene.

Cystic Fibrosis↗
PubMed1986

Amphetamine potentiation of anti-conflict action of chlordiazepoxide.

A modified Geller-Seifter paradigm was employed to test in male albino rats the effects of subthreshold doses of amphetamine and chlordiazepoxide (CDP), administered separately or in combination, on shock induced suppression of food-reinforced lever-pressing. MK-801, a newly synthesized sympathomimetic with anxiolytic and anticonvulsant properties, was also tested. dl-Amphetamine in doses of 0.1, 0.2, 0.3, and 1.0 mg/kg had no anxiolytic nor anxiogenic effects, but at 1.0 mg/kg it increased non-conflict responding. CDP in doses of 0.1, 0.2, and 0.4 mg/kg had no significant effect on conflict and non-conflict responding. CDP in the dose of 0.8 mg/kg tended to increase conflict responding. Coadministration of amphetamine (0.2 mg/kg) and CDP (0.4 mg/kg) had a significant anti-conflict effect. MK-801 at 50 micrograms/kg and 100 micrograms/kg caused a significant increase in non-conflict responding. MK-801 at 50 micrograms/kg exerted also a significant anti-conflict effect. The disinhibitory effects of amphetamine coadministered with CDP were discussed in terms of a possible enhanced noradrenergic or dopaminergic activity and their interaction with GABA neurotransmission at GABA-benzodiazepine coupled sites.

Amphetamine↗
PubMed1983

Anticonflict action of sodium valproate. Interaction with convulsant benzodiazepine (Ro 5-3663) and imidazodiazepine (Ro 15-1788).

The possibility that Ro 15-1788, a specific benzodiazepine antagonist would reverse the anxiolytic effect of VPA (200 mg/kg) in the Geller-Seifter paradigm was tested, using male albino rats. VPA (200 mg/kg) induced disinhibition which was antagonized by a convulsant benzodiazepine, Ro 5-3663 (1 mg/kg), but not by imidazobenzodiazepine, Ro 15-1788 at doses of 10 mg/kg, or 30 mg/kg. However, Ro 15-1788 (30 mg/kg) did have a short lasting antagonistic effect on VPA when tested in a "condensed" form (see text) of the conflict test. The nature of the anticonflict potency of VPA is discussed.

Animals↗
PubMed1983

A behavioral examination of convulsant benzodiazepine and GABA antagonist, Ro 5-3663, and benzodiazepine-receptor antagonist Ro 15-1788.

The potential "anxiogenic" effects of convulsant benzodiazepine and GABA-antagonist, Ro 5-3663 and specific antagonist of benzodiazepine receptors, Ro 15-1788 were compared in the Geller-Seifter conflict paradigm. Chlordiazepoxide (CDP) (5 mg/kg) was used as a "positive" control. Both Ro 5-3663 (1 mg/kg) and Ro 15-1788 (10 mg/kg) antagonized the anticonflict effect of CDP. However, while Ro 15-1788 had a modest anticonflict potency. Ro 5-3663 had an anxiogenic effect in its own right.

Animals↗