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S Stahl

Publications and source records attributed to S Stahl.

At least 37 records · Page 2Linked to original sources

Serotonin and anxiety: current models.

Evidence for the importance of the serotonin system in anxiety disorders has increased substantially in recent years. Although preclinical research has provided an important source of hypotheses, clinical work on the value of selective serotonin reuptake inhibitors (SSRIs) in these conditions has been particularly persuasive. In this paper, a number of models of serotonin in the anxiety disorders are reviewed, and the clinical advantages of the SSRIs in anxiety disorders are emphasized. Models of serotonin in anxiety disorders include: 1) a 'see-saw model'; 2) an 'amygdala model'; and 3) a 'basal ganglia model'. While any simplistic schema in this complex area must fail, these various models have some heuristic value for the clinician. From a clinical perspective, the availability of the SSRIs has proved a significant step forward in the treatment of the anxiety disorders such as panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, and social anxiety disorder (social phobia); certainly these agents offer several advantages over previously existing pharmacotherapeutic alternatives such as the benzodiazepines and tricyclic antidepressants.

Animals↗

Hybrid external fixation in high-energy elbow fractures: a modular system with a promising future.

BACKGROUND: Severe, high-energy, periarticular elbow injuries producing a "floating joint" are a major surgical challenge. Their reconstruction and rehabilitation are not well documented. Therefore, the following reports our experience with treating such injuries caused by war wounds. METHODS: Seven adults with compound open peri- and intra-articular elbow fractures were treated in hybrid ring tubular fixation frames. After debridement, bone stabilization, and neurovascular reconstructions, early controlled daily movements were started in the affected joint. RESULTS: These seven patients had together seven humeral, five radial, and six ulnar fractures. All fractures united at a median time of 180 days. No deep infection developed. The functional end results assessed by the Khalfayan functional score were excellent in two, good in one, and fair in four of these severely mangled upper extremities. None was amputated. CONCLUSIONS: The Mangled Extremity Severity Score has been shown to be unable to provide a reliable assessment for severe high-energy limb injuries surgically managed with the modular hybrid thin wire tubular external fixation system. This hybrid system is a very useful addition to the surgical armamentarium of orthopedic trauma surgeons. It both allows complex surgical reconstructions and reduces the incidence of deep infections in these heavily contaminated injuries. The hybrid circular (thin wire) external fixation system is very modular and may provide secure skeletal stabilization even in cases of severely comminuted juxta-articular fractures on both sides of the elbow joint (floating elbow) with severe damage to soft tissues. This fixation system allows individual fixation of forearm bone fractures, thus allowing the preservation of pronation-supination movements.

Adult↗

Anterior interosseous nerve palsy associated with Galeazzi fracture.

Galeazzi fracture is more common in adults than in children. Associated neurologic deficits are rare and easily missed at the first clinical examination. The authors describe a case of anterior interosseous nerve palsy after closed Galeazzi fracture. Conservative treatment resulted in complete return of normal nerve function, suggesting that this is a neurapraxia type of injury.

Child↗

Production of cis-1,2-dihydroxy-3-methylcyclohexa-3,5-diene (toluene cis glycol) by Rhodococcus sp. MA 7249.

An attractive method for producing cis-1,2-dihydroxy-3-methylcyclohexa-3,5-diene (toluene cis glycol) was developed employing a cis dihydrodiol dehydrogenase "deficient" strain of Rhodococcus (MA 7249). The toluene cis glycol produced was found to have optical rotations of [alpha]D25 = +25.8 (c 0.45, CH3OH) and +72.8 (c 0.42, CHCl3) which indicated an absolute configuration of (1S,2R) when compared with previously published values. When cultivated in laboratory fermentor in the presence of toluene vapors, MA 7249 reached a toluene cis glycol concentration up to 18 g/l in 110 h. Culture MA 7249 also accumulated cis (1S,2R) dihydrodiols from dihydronaphthalene, biphenyl, chlorobenzene, and styrene.

Journal Article↗

Loss of postsynaptic GABA(A) receptor clustering in gephyrin-deficient mice.

The tubulin-binding protein gephyrin, which anchors the inhibitory glycine receptor (GlyR) at postsynaptic sites, decorates GABAergic postsynaptic membranes in various brain regions, and postsynaptic gephyrin clusters are absent from cortical cultures of mice deficient for the GABA(A) receptor gamma2 subunit. Here, we investigated the postsynaptic clustering of GABA(A) receptors in gephyrin knock-out (geph -/-) mice. Both in brain sections and cultured hippocampal neurons derived from geph -/- mice, synaptic GABA(A) receptor clusters containing either the gamma2 or the alpha2 subunit were absent, whereas glutamate receptor subunits were normally localized at postsynaptic sites. Western blot analysis and electrophysiological recording revealed that normal levels of functional GABA(A) receptors are expressed in geph -/- neurons, however the pool size of intracellular GABA(A) receptors appeared increased in the mutant cells. Thus, gephyrin is required for the synaptic localization of GlyRs and GABA(A) receptors containing the gamma2 and/or alpha2 subunits but not for the targeting of these receptors to the neuronal plasma membrane. In addition, gephyrin may be important for efficient membrane insertion and/or metabolic stabilization of inhibitory receptors at developing postsynaptic sites.

Animals↗

Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice.

Fabry disease is an X-linked metabolic disorder caused by a deficiency of alpha-galactosidase A (alpha-Gal A). The enzyme defect leads to the systemic accumulation of glycosphingolipids with alpha-galactosyl moieties consisting predominantly of globotriaosylceramide (Gb3). In patients with this disorder, glycolipid deposition in endothelial cells leads to renal failure and cardiac and cerebrovascular disease. Recently, we generated alpha-Gal A gene knockout mouse lines and described the phenotype of 10-week-old mice. In the present study, we characterize the progression of the disease with aging and explore the effects of bone marrow transplantation (BMT) on the phenotype. Histopathological analysis of alpha-Gal A -/0 mice revealed subclinical lesions in the Kupffer cells in the liver and macrophages in the skin with no gross lesions in the endothelial cells. Gb3 accumulation and pathological lesions in the affected organs increased with age. Treatment with BMT from the wild-type mice resulted in the clearance of accumulated Gb3 in the liver, spleen, and heart with concomitant elevation of alpha-Gal A activity. These findings suggest that BMT may have a potential role in the management of patients with Fabry disease.

Aging↗

Elevated expression of endoglin, a component of the TGF-beta-receptor complex, correlates with proliferation of tumor endothelial cells.

Endoglin/CD105 is a membrane protein involved in the TGF-beta receptor signalling pathway. Endoglin expression has been reported to be selective for a few cell types, in particular endothelial cells, although a number of conflicting reports have been published. In this study, we performed a detailed analysis of endoglin expression in human lung tumors and different tumor and endothelial cell lines, employing reverse-transcriptase-polymerase-chain reaction as well as immunoblotting and immunohistochemistry using verified antibodies to endoglin. Our data show a clearly preferential expression of both endoglin mRNA and protein in endothelial cells. In tumors, endoglin expression was strongly elevated in the angiogenic endothelium at the tumor edges. In agreement with this observation, we find a clear correlation between endoglin expression and markers of proliferation, such as cyclin A and Ki-67, suggesting that endoglin expression is linked to cell-cycle regulation. These findings not only resolve some of the discrepancies in the literature, but also provide the basis for further applications making use of its selective localization and expression in the tumor vasculature.

Antigens, CD↗

Effects of nucleoside analog incorporation on DNA binding to the DNA binding domain of the GATA-1 erythroid transcription factor.

We investigate here the effects of the incorporation of the nucleoside analogs araC (1-beta-D-arabinofuranosylcytosine) and ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl] guanine) into the DNA binding recognition sequence for the GATA-1 erythroid transcription factor. A 10-fold decrease in binding affinity was observed for the ganciclovir-substituted DNA complex in comparison to an unmodified DNA of the same sequence composition. AraC substitution did not result in any changes in binding affinity. 1H-15N HSQC and NOESY NMR experiments revealed a number of chemical shift changes in both DNA and protein in the ganciclovir-modified DNA-protein complex when compared to the unmodified DNA-protein complex. These changes in chemical shift and binding affinity suggest a change in the binding mode of the complex when ganciclovir is incorporated into the GATA DNA binding site.

Animals↗

Chronic tophaceous gouty arthritis mimicking rheumatoid arthritis.

OBJECTIVES: To analyze the factors which differentiate chronic tophaceous arthritis from rheumatoid arthritis. METHODS: We describe two cases of chronic gouty arthritis masquerading as rheumatoid arthritis. The characteristic features of each of these two conditions and the diagnostic approach are discussed in light of relevant literature. RESULTS: The correct diagnosis was reached by the combination of accurate history taking (family history of gout, alcoholism, previous diuretic therapy and renal stones), guiding clinical features (subcutaneous tophaceous deposits) and specific radiological (assymetrical erosions with sclerotic margins and overlying edges) and laboratory findings (hyperuricemia and hyperuricosuria). It was confirmed by the identification of monosodium urate (MSU) crystals in the synovial and subcutaneous tissues. CONCLUSIONS: Gout and rheumatoid arthritis rarely coexist. Chronic gouty arthritis may mimic rheumatoid arthritis, and vice-versa. Clinical suspicion supplemented by characteristic laboratory, radiological and histologic findings help at reaching an accurate diagnosis.

Arthritis, Gouty↗

A group motivational treatment for chemical dependency.

Patient "motivation" has been implicated as a critical component in addiction treatment outcomes. To date, treatments utilizing motivational elements have been conducted as individual interventions. We describe the development of a Group Motivational Intervention (GMI), a four-session, manual-driven group approach that employs key hypothesized motivational elements. These include the six motivational elements derived by Miller and Sanchez (1994) from successful alcoholism treatments, described with the acronym, FRAMES (feedback, responsibility, advice, menu of options, empathy, and self-efficacy). GMI is additionally informed by concepts derived from "self-determination theory" (Deci & Ryan, 1985), concerned with understanding motivation as either internal/autonomous or external/controlled. Evidence indicates that people will value and persist longer in behaviors that they perceive as autonomously motivated. GMI techniques utilize the interpersonal factors found to be autonomy-supportive in self-determination theory. Preliminary results from a randomized clinical trial suggest that key motivational processes are affected by GMI: patients perceive the GMI environment and group leader as significantly more "autonomy supportive" than treatment "as usual."

Alcoholism↗

Asymmetric direduction of 1,2-indanedione to cis (1S,2R) indanediol by Trichosporon cutaneum MY 1506.

Cis (1S,2R) indanediol is a potential precursor to (-)-cis (1S,2R)-1-aminoindan-2-ol, a key chiral synthon for a leading HIV protease inhibitor, Crixivan (Indinavir). A potential route to the biosynthesis of this important precursor, the microbial asymmetric direduction of 1,2-indanedione to its corresponding diol, cis (1S,2R) indanediol, was investigated. The screening of 32 yeast strains yielded Trichosporon cutaneum MY 1506 as a suitable biocatalyst. At the 2-l shake-flask scale, 1,2-indanedione (charged at 1.0 g/l) was bioconverted to cis (1S,2R) indanediol at a final bioconversion yield of 99.1% and an enantiomeric excess of >99%. When scaled up in a 23-l bioreactor, T. cutaneum produced 8.4 g of pure cis (1S,2R) indanediol, and the isolated yield of cis (1S,2R) indanediol was 52%. Purification of the scale-up also yielded 0.9 g of the more polar trans (1S,2R) indanediol diastereomer, a minor bioreduction product. Supercritical fluid chromatography analyses of the purified cis (1S,2R) and trans (1S,2S) indanediol demonstrated that the enantiomeric excesses during this bioconversion scale-up were 99% and 26%, respectively.

Journal Article↗

Immediate autografting of bone in open fractures with bone loss of the hand: a preliminary report. Case reports.

Three patients with open fractures of the hand associated with bone loss were treated within four to six hours of injury by corticocancellous bone grafting and soft tissue coverage after meticulous debridement, copious irrigation of the wounds, and broad-spectrum antibiotics given intravenously. Long term follow-up was uneventful and showed that the graft had taken and healed well with early and full restoration of function and a good cosmetic result. Immediate corticocancellous bone grafting of an injured hand could be used in selected cases with well-debrided, surgically clean wounds as long as there is a rich blood supply. Adequate bone fixation, soft tissue coverage, and broad-spectrum antibiotics given intravenously will remove the risk of infection. Hand architecture is corrected while wound contracture and secondary deformity are avoided. Both patients' discomfort and hospital costs are considerably reduced.

Adult↗

Flexor tendon lengthening in zone II injuries.

Primary repair of acute severed flexor tendons in zone II has replaced the "no-man's-land" concept, which advocates secondary procedures. Primary repair can be difficult when there are severe soft-tissue and bony injuries, and may lead to unfavorable results. The authors describe a technique that is simple, quick, and safe, and eliminates the need for tendon harvesting or other secondary procedures. It can also be used when a flexor profundus tendon gap occurs due to the injury.

Adult↗

Monomer-trimer equilibrium of the ectodomain of SIV gp41: insight into the mechanism of peptide inhibition of HIV infection.

The monomer-trimer equilibrium of the ectodomain of SIV gp41 (residues 27-149, e-gp41) has been characterized by analytical ultracentrifugation, circular dichroism (CD), and NMR spectroscopy. Based on analytical ultracentrifugation experiments performed at different rotor speeds and protein concentrations, the equilibrium association constant for the SIV e-gp41 trimer is 3.1 x 10(11) M(-2). The presence of intermolecular nuclear Overhauser effects in a mixture of 12C and 13C-labeled e-gp41 prepared under nondenaturing conditions unambiguously demonstrates that there is a dynamic equilibrium between the monomer and trimer. The CD spectra taken as a function of SIV e-gp41 concentration suggest that the helical content of the monomeric state does not change significantly relative to that of the trimeric state. The relevance of the monomer-trimer equilibrium is discussed with respect to gp41 function and the inhibitory properties of gp41 peptides.

Anti-HIV Agents↗

Simultaneous Scaphoid and Galeazzi Fractures.

Among wrist injuries, scaphoid fractures are second only in number to fractures of the distal radius, while Galeazzi fractures are relatively infrequent. It is rare for the two fractures to occur concomitantly. We report such a case in a 65-year-old woman.

Journal Article↗

Digital nerve repair by autogenous vein graft in high-velocity gunshot wounds.

Gunshot wounds to the hands are high-energy injuries that cause widespread tissue damage, including to the nerves. Great difficulty is encountered in later reconstruction with nerve grafting of gaps in these destructive and scarred wounds. We present our experience with three patients with digital nerve repair by autogenous vein graft performed at an early stage in this type of injury. Based on our experience and that of others, this simple and rapid technique suggests a high rate of satisfactory results. It also avoids extensive and destructive late dissection and the morbidity associated with other late reconstructive procedures.

Adult↗