Search PubMed⌕ Search

Biomedical subjects

M Baron

Publications and source records attributed to M Baron.

At least 91 records · Page 5Linked to original sources

Congenital heart disease in the adult patient: the value of plain film chest radiology.

Congenital heart disease (CHD) is a major clinical problem in children, occurring in 0.8% of newborns (1). In the past, most patients with CHD died in infancy. With improved surgical and postoperative care, as well as more accurate preoperative evaluation, the overall 10-year survival rate is > 90%. As a result, > 500,000 adults in the United States have surgically treated CHD (2). In addition, at least 150,000 adults are thought to have unrecognized, misdiagnosed, or recognized but untreated CHD (3,4). Diagnostic imaging procedures for the evaluation of CHD include plain film radiology, fluoroscopy, angiocardiography, echocardiography, scintigraphy, computed tomography (CT), and magnetic resonance imaging (MRI). Each has unique as well as overlapping abilities to characterize precisely cardiovascular anatomy and pathophysiology. We emphasize those congenital cardiac disorders found predominantly in adults. In addition, conditions that are usually unrecognized in childhood, "slip through the system", and become clinically recognized in adults for the first time, often with an atypical clinical presentation, are discussed (5). The interpreter of the plain film radiograph has a unique opportunity to identify and often characterize the severity of a congenital cardiac disorder that may be unrecognized by the patient's physician. Important clues found on plain film radiographs will suggest either additional studies to pin-point the type of CHD more precisely or that no additional studies are needed because the recognized lesion is incidental and not of clinical significance.

Adult↗

Searching for complex disease genes: can it be made any easier?

The search for complex disease genes is gaining momentum. Recent guidelines for expediting this effort, such as "intelligent" genome scanning and statistical criteria for detecting weak signals indicative of linkage, are discussed, with special reference to psychiatric disorders.

Base Composition↗

Genes and psychosis: old wine in new bottles?

Despite initial setbacks, linkage studies with DNA markers continue to occupy center stage in psychiatric research. Advances in molecular and statistical techniques have revived the search for disease genes, leading to a new harvest of findings. Most interest in recent years has focused on potential linkages between schizophrenia and chromosomes X-Y (the pseudoautosomal region) and 22q12-13.1, and between bipolar affective disorder and chromosomes 18 (pericentromeric region) and 21q22.3. This article provides a critical evaluation of theses studies, with implications for future research. Concerns over earlier linkage trials make this scrutiny current and topical.

Bipolar Disorder↗

Variability of skin scores and clinical measurements in scleroderma.

OBJECTIVE: To determine the variability of several clinical outcome measurements commonly used in scleroderma clinical trials. METHODS: Ten researchers, members of a multicenter placebo controlled trial of methotrexate in early diffuse scleroderma, studied the intraobserver and interobserver variability of variables used to assess efficacy in scleroderma trials. RESULTS: For most measures, the variability within an observer was less than that found between observers, and therefore the intraobserver reliability was better than the interobserver reliability. The reliability of the modified Rodnan skin score exceeded the Rodnan skin score. Measures with inherent interpretation such as global assessments and skin scores had more variability than easily performed measurements such as grip strength and oral opening. CONCLUSION: Some of our variability was higher than variability previously reported; this could be due to the large number of examiners and patients in our study.

Female↗

Further characterization of the NH2-terminal fibrin-binding site on fibronectin.

The fibronectin (Fn) monomer contains two major sites of fibrin binding affinity present within the NH2-terminal and COOH-terminal domains; they consist of five (1F1-5F1) and three (10F1-12F1) consecutive type 1 modules, respectively. Recently, we have reported that the fourth and fifth type 1 module pair (4F1.5F1) of the NH2-terminal domain of fibronectin demonstrated fibrin binding ability (Williams, M. J., Phan, I., Harvery, T. S., Rostagno, A., Gold, L. I., and Campbell, I. D. (1994) J. Mol. Biol. 235, 1303-1311). In an attempt to further localize fibrin binding activity and to characterize the nature of the interaction between different type 1 modules of Fn and fibrin, we have tested a range of recombinant proteins and subtilisin generated proteolytic fragments of Fn in an enzyme-linked immunosorbent assay (ELISA) and by fibrin affinity chromatography. Of the recombinant proteins, we found that only the 4F1.5F1 exhibited significant fibrin binding activity, while 1F1, 1F1.2F1, 7F1, and 10F1 had little to no affinity for fibrin. On a molar basis, 4-5 times more 4F1.5F1 than a proteolytic fragment, corresponding to 1F1-5F1 (25.9 kDa) was required to cause 50% inhibition (IC50) of intact biotinylated Fn binding to fibrin in a competitive ELISA. This suggests that all five type 1 modules in tandem engender higher fibrin binding activity than the 4F1.5F1 alone. Furthermore, since fibrin binding activity of the intact Fn molecule was inhibited, by 70-80%, by the 4F1.5F1, the 25.9-kDa fragment, and a MoAb mapped to an epitope on the 4F1.5F1, the fibrin-binding site within the 4F1.5F1 contributes greatly to the non-covalent interaction of intact Fn with fibrin. These results provide significant insight into the Fn/fibrin interaction, a major component of the processes of wound repair and fibrin matrix assembly.

Amino Acid Sequence↗

Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia. A randomized, double-blind clinical trial.

OBJECTIVE: To compare the relative efficacy and tolerability of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia, and to identify predictors of response to amitriptyline and cyclobenzaprine. METHODS: Two hundred eight patients who fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia were entered into a 6-month prospective, double-blind, multicenter trial and were randomized to 1 of 3 treatment groups: amitriptyline, cyclobenzaprine, or placebo. RESULTS: After 1 month, 21%, 12%, and 0% of the amitriptyline, cyclobenzaprine, and placebo patients, respectively, had significant clinical improvement (amitriptyline versus placebo P = 0.002, cyclobenzaprine versus placebo P = 0.02, amitriptyline versus cyclobenzaprine P not significant). These percentages increased to 36%, 33%, and 19%, respectively, at the 6-month assessment (P not significant). The nature and frequency of side effects reported by patients treated with amitriptyline and those reported by patients treated with cyclobenzaprine were similar. A normal Minnesota Multiphasic Personality Inventory (MMPI) profile at baseline was predictive of clinical improvement at the 1-month evaluation (odds ratio 3.3, 95% confidence interval 1.2-9.0). However, neither the MMPI profile nor any of the demographic, clinical, or functional parameters evaluated at baseline predicted long-term response. CONCLUSION: Our data confirm the short-term efficacy of amitriptyline and cyclobenzaprine in a small percentage of patients with fibromyalgia. Long-term efficacy could not be demonstrated because of a higher-than-expected placebo response. Predictors of response to these drugs could not be determined.

Amitriptyline↗

PCR protocol- and inulin catabolism-based differentiation of inulinolytic soil bacteria.

Bacteria collected from rotting dahlia tubers, instead of degrading inulin to D-fructose, preferentially formed the known DFA III (beta-2.1': alpha-2',3 difructofuranose anhydride), inulobiose, higher inulo-oligosaccharides, and exoheteropolysaccharides. Owing to the morphological and Gram staining variability, the bacterial isolates designated YLW and CRM were examined to differentiate them from a reference strain Arthrobacter ureafaciens. The comparative analyses were whole DNA random amplification by Taq polymerase (RAPD-PCR protocol), culture media DFA III content in culture media, chromatographic profile of oligosaccharides formed, and exopolysaccharide fractionation/fragmentation. A comparative study in liquid shake cultures showed that the isolate YLW was faster than the reference strain in the production of DFA III when the inulin/yeast extract ratio was maintained at 10 in the medium, although a similar maximum yield was displayed with both bacteria (13-14 mg of DFA/mL cell free media from the initial 30 mg/mL of inulin load). Doubling the yeast extract input, an even faster onset of DFA III production occurred with YLW but with no further improvement in the maximum yield. Both strains further degraded the resulting DFA during the stationary growth phase. The main ability of CRM when grown on inulin was the production of exopolysaccharides, although culture condition variation also allowed DFA III production, which was accompanied by somewhat lower amounts of its reducing analog, inulobiose.

Arthrobacter↗

A pedigree series for mapping disease genes in bipolar affective disorder: sampling, assessment, and analytic considerations.

A series of 57 extended pedigrees with high density of bipolar affective disorder is described. Ascertainment and diagnostic procedures are documented and simulation studies to assess statistical power are carried out. The pedigrees, obtained in the US and Israel, are comprised of 1508 adult individuals with best estimate consensus diagnoses (12-71 relatives per pedigree), 490 of whom (including 401 sib pairs) meet criteria for a conservative disease definition (bipolar disorder or recurrent major depression). Cell lines have been established on 1324 of these individuals. Statistical power to detect linkage with lod score analysis, assuming autosomal dominant transmission and highly polymorphic DNA markers, is nearly 100% for alpha (proportion of linked families) = 30%, and 75% for alpha = 20%. This is the largest bipolar pedigree series reported to date; its unique features make it amenable to various gene detection techniques.

Bipolar Disorder↗

Secondary structure of a pair of fibronectin type 1 modules by two-dimensional nuclear magnetic resonance.

The fourth and fifth type 1 module pair, corresponding to residues 151-244 from the amino terminus of human fibronectin, has been produced as a recombinant protein using a yeast expression system and studied by two-dimensional homonuclear 1H nuclear magnetic resonance (NMR) spectroscopy. The sequence-specific resonance assignment of the 1H NMR spectrum has been completed using a combination of 2D 1H nuclear Overhauser effect (NOE) spectroscopy, homonuclear Hartmann-Hahn, and correlated spectroscopy spectra recorded under a variety of pH and temperature conditions. Slow exchanging amide protons have been identified and estimates of many backbone 3JNH-C alpha H coupling constants were obtained by line shape fitting. The secondary structures of each module conform closely to the "consensus" fibronectin type 1 module structure determined previously for two other single type 1 modules. In the module pair described here, the two modules are linked by a short five-residue linker which appears to form a turn. The intermodule interface is defined by NOEs observed between a hydrophobic three-residue sequence from the fourth type 1 module and residues in the first double-stranded beta-sheet of the fifth type 1 module. The interaction is dominated by a tryptophan residue (unconserved in other type 1 sequences) within the fourth module, which causes large upfield ring current shifts for several proton resonances from the beta-sheet of the fifth module. The NMR data indicate that there is little or no relative reorientation of the two modules about the linker region but rather that the two modules combine with a fixed and intimate hydrophobic contact.

Amino Acid Sequence↗

Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees.

The hypothesis that chromosomal region Xq27-28 harbours a gene for manic-depression has been a focus of interest in human genetics. X-linked inheritance of manic depressive illness has been re-examined in 3 multigeneration Israeli kindreds. Extension and re-evaluation of pedigree data, including new individuals, diagnostic follow-up, and analysis with DNA markers, shows greatly diminished support for linkage to Xq28. The peak lod scores in two of the pedigrees have dropped several lod units to clearly negative values at the RCP-F8-G6PD gene cluster. On the other hand, positive lod scores (Zmax = 2.09) are sustained in another pedigree at the same map location. None of the pedigrees show linkage to more proximal markers, including the Xq27 locus DXS98. Our analysis underscores the uncertainties in studying complex disorders.

Adult↗

Laparoscopy in adnexal pathology in the child: a study of 28 cases.

We report our experience with laparoscopy in adnexal pathology in the child. Twenty-eight children (mean age 13 years; range 8 to 16) underwent 30 laparoscopy procedures. Therapeutic laparoscopy was performed in 3 cases: transposition of an ovary before radiotherapy, bilateral gonadal excision for Turner's syndrome and ovarian fixation after contralateral torsion of normal adnexa (TNA). Diagnostic and potentially therapeutic laparoscopy was performed in 25 cases: 12 suspected torsion of adnexa (6 confirmed), 4 possible ovarian or appendicular pathology (1 appendicitis), 4 to confirm the histological nature of an ovarian tumor (2 functional cysts, 1 old TNA, 1 dermoid cyst), 3 suspected salpingitis (2 confirmed), and 2 chronic pelvic pain (1 endometriosis). No pathology was found in 2 cases, and in 1 case pelvic adhesions prevented confirmation of the diagnosis. Thirteen laparoscopically-guided surgical acts were performed: 2 detorsions of adnexa, 2 excisions of necrosed adnexa and 9 punctures with or without biopsy for functional cysts. Intralaparoscopic detorsion of TNA was complicated in one case by fibrinolysis requiring secondary laparotomy. Mean hospitalisation was 3 days (range 1 to 16). the preferential therapeutic indications for laparoscopy in the child are transposition of an ovary and ablation of the gonads in case of sexual ambiguity. It is used diagnostically in cases of sudden pelvic pain. In addition to this diagnostic role, it now allows most treatments to be carried out (detorsion with or without fixation, transparietal cystectomy), including those for associated lesions (appendicectomy). Its morbidity is quite low, which warrants increasing the number of indications in pediatric pathology.

Adolescent↗

[Incidence of the form and caliber of urethral resistance. Evaluation for a normal masculine urethra and in cases of obstruction due to prostatic hypertrophy].

Certain forms of benign prostatic hypertrophy are associated with a reduction of the calibre of the prostatic urethra of the median lobe, a defect of infundibulisation of the bladder neck and a dilated appearance of the bulbar urethra. The objective of this study was to verify whether hydrodynamic arguments could be used to confirm the concept that defective infundibulisation of the bladder neck is directly responsible for an obstructive syndrome or via a reduction in the calibre of the bladder neck orifice. More generally, this study was designed to quantify the distribution of resistance to flow along the normal urethra and to define the role of cervicoprostatic and urethral deformities in the obstruction associated with benign prostatic hypertrophy. Urodynamic studies are unable to answer this question, as the instantaneous urethral resistance is evaluated globally by the Pressure-Flow relation. The authors performed morphological analysis to divide the urethra into simple hydraulic segments for which the corresponding pressure drop coefficients were calculated. These coefficients constitute an approach to segmental resistance to flow and can be used to quantify changes in shape observed on voiding urethrography or ultrasonography. Digital analysis of voiding urethrographies showed that, under normal conditions, urethral resistance was regularly distributed along the urethra and essentially depended on friction of the urethral wall. In the case of benign prostatic hypertrophy, even with a median lobe, the increase in the pressure drop coefficients was due to a reduction in the calibre of the bladder neck orifice and prostatic urethra. Cervical deformities appeared to be minimally obstructive, according to urodynamic parameters, if they were not associated with a reduction in the calibre of the bladder neck orifice.

Evaluation Studies as Topic↗