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Biomedical subjects

R Frank

Publications and source records attributed to R Frank.

At least 181 records · Page 10Linked to original sources

Rural mental health coverage under health care reform.

Efforts to integrate services and financing under health care reform hold benefits for provision of services to rural mentally ill persons. Remote areas pose a particular challenge as the unique characteristics of rural America are even more evident. The model for managed care in remote rural areas will differ from those used in urban and their adjacent rural areas. Universal coverage would remove the barriers to accessing care for this population, but does not assure availability of adequate mental health services are or providers in rural areas. Characteristics of currently available rural mental health services are presented and obstacles to expanded delivery under health care reform are outlined.

Community Mental Health Services↗

Spot synthesis of overlapping peptides on paper membrane supports enables the identification of linear monoclonal antibody binding determinants on morbillivirus phosphoproteins.

In order to map antigenic domains on the P-protein of morbillivirus, a series of overlapping peptides, representing the P-protein sequences of phocid distemper virus strain 2558/Han88 and canine distemper virus strain Onderstepoort, were synthesized on a paper support by the spot-technique. The reactivity of six monoclonal antibodies with the peptides was tested in an enzyme immunoassay and compared to their reactivity in Western blots and in an ELISA using detergent extracts from virus-infected cells. Three linear determinants could be localized on the P-protein. Two antibody-binding sites were delineated within the C-terminal (between amino acids 307-322 and 382-400, respectively), and a third one was located on the N-terminal part (amino acids 13-31) of the protein. Fine mapping of this binding site revealed that this was a part of an antigenic domain. In Western blots, the monoclonal antibodies reacting with this domain also reacted with a second protein which was possibly the V-protein.

Amino Acid Sequence↗

Acute exposure to acid fog: influence of breathing pattern on effective dose.

Concern about the possible adverse health effects of acid fog has been fed by two observations: air pollution disasters earlier in this century were typically associated with fog, and current samples of fog water can be strongly acid. To study the acute effects of acid fog on the lung, the authors generated a monodisperse 10 microM MMAD aerosol of H2SO4 with a pH of 2.0 and a nominal concentration of 500 micrograms/m3. They exposed seven healthy young men on alternate days to acid or control equiosmolar NaCl aerosol during 40 min of resting ventilation and 20 min of exercise; the latter was sufficiently intense to induce oronasal breathing. Exposure was by means of a head dome, a head-only exposure device that permitted continuous measurement (unfettered breathing) of Vr, f, VE, and the onset and persistence of oronasal breathing. In this article the authors compare the relative importance of parameters contributing to the between-subject variability in estimated hydrogen ion dose to the lower airways (H+LAW), based on analysis of variance. Physiologic parameters accounted for 70% of the variability, of which 34% was due to differences in duration of oronasal breathing (tON) and 36% to differences in ventilation rate during oronasal breathing (VE(ON)); inhaled hydrogen ion concentration [H+], the environmental parameter, contributed only 30%. Minute ventilation at the time of transition from nasal to oronasal breathing varied significantly among subjects even if normalized to FVC, an index of lung size.

Acid Rain↗

Preliminary evaluation of a dual chamber pacemaker with bradycardia diagnostic functions.

Unexplained syncope is the main indication for the implantation of a diagnostic pacemaker. Studies on those implanted have shown that in patients with unexplained syncope, the diagnosis of paroxysmal bradycardia was feasible and reliable. The present study was designed to evaluate a new bradycardia diagnosis algorithm, loaded in a dual chamber pacemaker, in 24 patients considered as candidates for diagnostic pacemakers. During a mean follow-up of 153 days, at least one bradycardia episode was recorded in 13 patients. The mean number of detected bradycardias was 6 and the median was 3. The mean delay between the algorithm activation and the first bradycardia episode was 67 days. The mechanism of bradycardia was atrioventricular block in 6 patients, sinus node dysfunction in 6 patients, and consecutive blocked atrial premature beats in 1 patient, as indicated by the event markers. In 11 patients bradycardia was recorded during the daytime only or day and night. In two patients the episodes were recorded only at night. Overall, the algorithm was well-tolerated; however, some mild symptoms were observed due to the method of bradycardia determination, allowing bradycardia. Three patients were symptomatic as a direct result of the algorithm operation, and four patients had symptoms related to the single chamber operation of the pacemaker while functioning in the diagnosis mode (VDI). These symptoms were relieved with DDD pacing.

Aged↗

Molecular cloning and characterization of NF-IL3A, a transcriptional activator of the human interleukin-3 promoter.

To isolate transcription factors important in the regulation of the human interleukin-3 (IL-3) gene, we screened a lambda gt11 cDNA library, constructed from phytohemagglutinin-stimulated human T-cell RNA, with a probe containing regulatory sequences in the upstream region of the IL-3 gene (located from bp -165 to -128 and referred to as the DNase I footprint A region). We isolated a 0.96-kb cDNA that encoded a basic amino acid domain and a leucine zipper domain and used the "rapid amplification and cloning of 3' ends" technique to isolate the 3' half of the cDNA clone, generating a 1.9-kb full-length cDNA clone. Using in vitro-translated protein, which we call NF-IL3A, we defined the IL-3 promoter sequences bound by NF-IL3A in DNase I footprinting assays as TAATTACGTCTG and, using gel shift assays, defined ATTACG as the minimal sequence required for binding of NF-IL3A in vitro. Proteins that bind to the NF-IL3A binding site are found in both unstimulated and stimulated T-cell lines in similar amounts, although the level of NF-IL3A mRNA increases after T-cell activation in several mature T-cell lines. The NF-IL3A protein is nearly identical to a recently identified transcriptional repressor protein, E4BP4, and NF-IL3A binds specifically to regulatory sequences in both the adenovirus E4 promoter and the human gamma interferon promoter. Cotransfection experiments demonstrate that introduction of an expression vector containing the NF-IL3A cDNA into resting T cells transactivates IL-3 promoter-chloramphenicol acetyltransferase gene plasmids that contain the A region; this effect requires the presence of an intact NF-IL3A binding site. One or more copies of the A region also confer NF-IL3A responsiveness on a heterologous promoter in T cells. NF-IL3A appears to play an important role in the expression of IL-3 by T cells.

Amino Acid Sequence↗

Response to acute ozone exposure in healthy men. Results of a screening procedure.

We screened 64 healthy, nonsmoking men, 18 to 35 yr old, for their sensitivity to 0.35 ppm ozone (O3) administered for 130 to 150 min with intermittent exercise. The changes in FVC, FEV1, AND FEF25-75 (p < 0.0001) immediately after O3 exposure varied widely among subjects. Histograms of the percentage changes in FVC and FEV1 did not differ from a unimodal, skewed (gamma) distribution (p = 0.99 and p = 0.17, respectively); the changes in FEF25-75 tended to deviate from a gamma distribution (p = 0.055). To adjust FEF25-75 for the confounding effects of O3 on FVC, we used multiple linear regression analysis with contemporaneous FVC as a covariable, analysis of a subgroup of nine subjects whose O3-induced FVC changes were < or = 5%, and volume correction of FEF25-75 for any changes in FVC after exposure. These analyses showed reductions in FEF25-75 unexplained by and following a different time course than the O3-induced changes in FVC. In 26 subjects also exposed to filtered air, significant effects of O3 on respiratory frequency (p < 0.004) and tidal volume (p < 0.0007) correlated weakly with FVC changes. The results confirm the wide variability in spirometric responsiveness among individuals to O3 and suggest that intrinsic narrowing of the small airways may be a significant component of the functional response.

Adolescent↗

Evidence for ozone-induced small-airway dysfunction: lack of menstrual-cycle and gender effects.

Recently, we analyzed FEF25-75 isovolumetrically to assess the acute effects of ozone (O3) on small-airway function: the reduction in isovolumetric (isoV) FEF25-75 at end exposure progressed during the next 25 min even as FVC was recovering. To evaluate this effect over a longer period, we measured isovolumetric FEFs, helium-oxygen (He-O2) volume of isoflow (VisoV), the multiple breath nitrogen washout (MBNW) curve, FRC, and RV in 24 subjects 24 h after a 130-min exposure to filtered air (FA) and O3 (0.35 ppm). Men and women were studied to test for gender-based differences in response, after first determining that menstrual-cycle phase did not itself influence response. Isovolumetric FEF25-75, Vmax50, and Vmax75 were reduced about equally at 25 min after O3 exposure (p < or = 0.02) and showed no recovery at 24 h. FVC and FEV1, although still depressed after 24 h (p < 0.05), showed substantial recovery (p < 0.01). FRC, RV, and VisoV showed no effect of O3 exposure. No gender differences in O3 responsiveness were found. In summary, O3-induced reductions in isovolumetric flow rates, suggestive of small-airway dysfunction, may persist for 24 h following acute exposure to O3, a time-course consistent with inflammation.

Adolescent↗

Ozone exposure in humans: inflammatory, small and peripheral airway responses.

We exposed eight normal adults to filtered air (FA) and 0.35 ppm ozone (O3) and compared responses in spirometry, including isovolume (isoV) flows at intermediate-to-low lung volumes, against levels of inflammatory markers in bronchoalveolar lavage fluid (BALF) and peripheral lung resistance (Rp) measured through a wedged bronchoscope. Spirometry was performed at the end, 25 min and 24 h after exposure, bronchoscopy at 24 h after exposure. The percentages of neutrophils, fibrinogen, albumin, PGE2, PGF2 alpha, and kinins were elevated in BALF after O3 compared with FA. The percentage reduction in (isoV) FEF25-75 at 25 min and 24 h after administration of O3 correlated closely with the rise in fibrinogen concentrations in BALF, a marker of altered vascular permeability. Rp, a measurement dominated by very small or peripheral airways, was unaffected in 7 of 8 subjects. The absence of change in Rp might have reflected insufficient penetration of O3 into these airways to produce or sustain an effect for 24 h; alternatively, the bronchoscopic procedure which included atropine and lidocaine pretreatment may have reversed an O3 effect. An unexpected finding was the significant association between baseline Rp (after FA) and the magnitude of the spirometric response to O3. Our results suggest that small airway dysfunction in the immediate post-O3 period is a marker of lung inflammation.

Adult↗

[Outcome of arrhythmogenic right ventricular dysplasia. Apropos of 4 cases].

The authors propose a classification of the outcome of arrhythmogenic right ventricular dysplasia with reference to 4 selected cases with a follow-up period of over 9 years. In type I, the left ventricular ejection fraction is normal (EF > 50%) and the risk, exclusively arrhythmic, can be controlled by appropriate antiarrhythmic therapy. This is the commonest form of arrhythmogenic right ventricular dysplasia with different varieties according to the degree of dilatation of the right ventricle. In type II, there is a variable degree of left ventricular involvement (30 < EF < 50%) either by extension of a comparable disease process as observed in the right ventricle or by an isolated or superimposed phenomenon of myocarditis. This form is stable and may remain stable for many years providing the arrhythmias are correctly treated. In type III, progressive degradation of the myocardium is observed over a period of about 10 years with a clinical presentation comparable to that of certain arrhythmogenic dilated cardiomyopathies which are often hereditary. In this case, the patients have an arrhythmic risk associated with that of cardiac failure which becomes progressively irreversible. The histology shows interstitial fibrosis with biventricular lymphocytic infiltration suggesting an autoimmune phenomenon. Therefore, the classification of cases of arrhythmogenic right ventricular dysplasia depends on the potential evolutivity of the lesions. When the patient is seen in the early stages of the disease, the prognosis should be garded, especially in a hereditary form.

Adult↗

Molecular mechanisms of APO-1/Fas(CD95)-mediated apoptosis in tolerance and AIDS.

The cell surface molecule APO-1/Fas(CD95), a member of the Tumor Necrosis Factor (TNF) receptor/Nerve Growth Factor (NGF) receptor superfamily mediates apoptosis upon cross-linking by agonistic antibodies or its ligand. Recent findings suggest that APO-1/Fas(CD95) and its ligand are the key molecules for antigen receptor-induced apoptosis in activated mature T cells. Here we propose a mechanism for antigen receptor-induced apoptosis of activated T cells via APO-1 ligand mediated autocrine suicide. This mechanism may also contribute to the depletion of CD4+ T cells in AIDS.

Acquired Immunodeficiency Syndrome↗

Idiopathic ventricular tachycardia: feasibility and efficacy of catheter ablation.

Idiopathic ventricular tachycardia is a well described syndrome of both left and right ventricular origin. This study reports the feasibility and efficacy of catheter ablation in this entity. Fourteen patients (mean age 30 +/- 10 years of age) and six patients (mean age 51 +/- 9 years of age) underwent endocardial catheter ablation with either direct-current shocks and radiofrequency energy, respectively. Earliest right and left ventricular activation and endocardial mapping during tachycardia were made to localize the site of ventricular tachycardia origin. The overall clinical efficacy was 93% for direct-current method with a mean number of shocks of 3.3 +/- 0.9/patient after a mean follow-up of 38 +/- 25 months. Radiofrequency ablation achieved an overall clinical efficacy of 83.6% with a mean of 3.2 pulses/patient during a follow-up of 10.5 +/- 4 months. The isoenzyme MB fraction of peak creatine kinase after ablation was less than 5%. There were no complications in any patient who underwent radiofrequency energy. Endocardial catheter ablation is feasible in patients with idiopathic ventricular tachycardia. Both methods are highly effective but radiofrequency energy is most desirable because of its lack of barotrauma, and may be considered as early therapy.

Adult↗

[Preliminary study of a double chamber pacemaker with diagnostic function].

Pacemakers with diagnostic functions have been implanted for several years. The main clinical indication for these devices is unexplained syncope. Some reports of the use of diagnostic pacemakers have shown that in patients with unexplained syncope, paroxysmal bradycardia was a common finding after implantation. Until recently, diagnostic functions were only available in VVI pacemakers, which explains the limitations of this type of function in determining the mechanism of the bradycardia. The aim of this study was to assess a new dual-chamber diagnostic pacemaker functioning in the VDI mode. Twenty-three patients were implanted with this type of unit and followed up for an average of 153 days. The number of episodes of bradycardia detected was 6 +/- 10 (median: 3). The interval between the installation of the algorithm and the date of the first episode of bradycardia was 67 +/- 86 days (range: 12-306 days). The mechanisms of the bradycardia were atrioventricular block (6 patients), sinus node dysfunction (6 patients) and blocked atrial bigeminy in 1 patient. These conclusions were drawn from analysis of chains of markers. Bradycardia was recorded during the day or during the day and night in 21 patients; bradycardia was exclusively nocturnal in only 2 patients. The tolerance of the algorithm was good on the whole but 3 patients reported minor symptoms related to the relative bradycardia inherent with this type of algorithm. Four other patients had a VDI pacemaker syndrome which was completely corrected by reprogramming the pacemaker to the standard DDD mode. These new devices represent a technical advance in the field of diagnostic pacemakers.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Munchausen syndrome by proxy].

The term "Munchausen by proxy" denotes a special form of factitious disorder and a rare kind of child abuse. We present the case of a 12-year-old boy, whose mother's manipulations culminated in his immobilization in a wheelchair and the implantation of a pacemaker. Problems of diagnosis and clinical management of Munchausen by proxy are discussed.

Adult↗

[Arrhythmogenic right ventricle: dysplasia or cardiomyopathy? Value of left ventricle ejection fraction].

The left ventricular ejection fraction (LVEF) of 76 patients suffering from arrhythmogenic dysplasia or cardiomyopathy of the right ventricle (ventricular tachycardia associated with structural abnormalities of the right ventricle) demonstrated two subgroups situated above and below 45%. Values of LVEF less than 45% were similar to those of a control population of 6 cases of idiopathic dilated cardiomyopathy with ventricular tachycardia of left ventricular origin (p = 0.2). These patients also have the same unfavourable long-term prognosis. Histological data obtained from four cases belonging to the group of patients with dysplasia or cardiomyopathy of the right ventricle with a low ejection fraction demonstrated the presence of signs of myocarditis involving both ventricles. This suggests that these patients may suffer from an infectious phenomenon superimposed on a specific histological substrate, which may lead to deterioration of their myocardial function. These results are in line with those of the literature. The term arrhythmogenic cardiomyopathy of the right ventricle should therefore be reserved to the subgroup of patients with an LVEF less than 45%. Finally, arrhythmogenic cardiomyopathy of the right ventricle appears to be a complication of dysplasia following the development of a myocarditic phenomenon. This may explain the wide range of clinical forms observed in patients with ventricular tachycardia of right ventricular origin associated with structural abnormalities of the right ventricle.

Adolescent↗

Neurothelin: amino acid sequence, cell surface dynamics and actin colocalization.

Neurothelin is a cell surface protein of chicken endothelial cells at the blood-brain barrier and also of pigment epithelial cells forming the blood-eye barrier. Peptide sequencing of affinity-purified neurothelin revealed that it is likely to be identical with the protein called HT7. It belongs to the immunoglobulin superfamily having two extracellular C2-type domains, a membrane spanning region and a cytoplasmic tail. During development neurothelin cell surface localization changed on pigment epithelial cells. In early embryogenesis neurothelin was found preferentially at lateral sites of neighboring epithelial cells, but after hatching, predominantly on basal cell surfaces and on apical microvilli of epithelial cells that contact retinal photoreceptors. Disruption of cell-cell contacts induced a rapid change of neurothelin distribution on the cell surface in vitro as could be shown by confocal laser microscopy. Disintegration of microfilaments by cytochalasin D hampered this specific cell surface rearrangement of neurothelin, whereas depolymerization of microtubules by demecolcine had no effect. In double-labeling experiments neurothelin and F-actin were colocalized. The data suggest that the polarized cell surface distribution of neurothelin is influenced intracellularly by F-actin and extracellularly by cell-cell interactions.

Actin Cytoskeleton↗

Evaluation of a porous bovine collagen membrane bandage for management of wounds in horses.

OBJECTIVE: To evaluate the effect of a porous bovine-derived collagen membrane (PBCM) on the rates of wound healing, cellular events, presence of granulation tissue, and appearance at termination of the study in surgically created full-thickness cutaneous wounds of the distal portion of the extremities of horses. DESIGN: Treated wounds (n = 12) received a PBCM dressing and control wounds were covered with a nonadherent dressing. Forelimbs and hind limbs were cross paired; the right forelimb and left hind limb always received the same dressing application, as did the left forelimb and right hind limb. Limbs pairs were then randomly assigned to 1 of the 2 dressings. ANIMALS: Six healthy male horses (3 sexually intact, 3 geldings) ranging from 2 to 10 (mean, 6.5) years and weighing between 278 and 568 (mean, 408.5) kg were studied. PROCEDURE: Full-thickness skin wounds (6.25 cm2) were created on the dorsal metatarsi and metacarpi of the experimental animals. A preformed PBCM dressing was evaluated in half the wounds (n = 12). Control wounds (n = 12) were dressed with a nonadherent gauze dressing. At each bandage change, wounds were subjectively assessed and were photographed, and measurements of horizontal and vertical wound dimensions were documented. Wound biopsy specimens obtained on days 2, 5, 7, 10, 21, and 31 were evaluated for presence of collagen, fibrin, inflammation, epithelium, and cellular elements of healing. Planar morphometry was used to determine total wound area and granulation area from the wound photographs. Percentage of contraction and epithelialization were calculated from these values. Linear regression analysis of the square root of the total wound area and the granulation area was performed. Wound area measurements were analyzed, using ANOVA for repeated measures. Regressions were compared, using covariance analysis and ANOVA. Significance was considered at P < 0.05. RESULTS: Fibrin score, neutrophil score, and degree of inflammation were significantly greater in the PBCM-treated wounds. No significant differences in the total wound, epithelialized, or contraction areas were detected between the PBCM-treated and control (nonadherent-treated) wounds. Rates of wound healing were not statistically different between the 2 treatment groups, though they were significantly slower in the hind limbs, compared with the forelimbs. Scabs were formed more frequently in the PBCM-treated wounds. CONCLUSIONS: Application of a porous collagen bandage was not detrimental to full-thickness cutaneous wound healing in horses.

Analysis of Variance↗

[Supraventricular tachycardia with wide QRS complexes during Vaughan-Williams class I anti-arrhythmic treatment. Diagnostic and therapeutic implications].

The authors report 8 cases of regular tachycardia with wide QRS complexes during treatment with Vaughan-Williams class 1 antiarrhythmic drugs. These antiarrhythmics, prescribed to prevent atrial fibrillation (3 patients) and atrial flutter (5 patients), were flecainide in 4 cases, propafenone in 2 cases and cibenzoline and hydroquinidine respectively associated with digitoxine and propranolol. These wide complex tachycardias were regular atrial tachycardias with 1/1 conduction to the ventricle. The action of the drug, more pronounced on intra-atrial conduction velocities than on atrioventricular node refractoriness resulted in transformation of flutter at 300 cycles/min with 2/1 conduction and a ventricular rate of 150 cycles/min to atrial flutter at 210 cycles/min with 1/1 ventricular conduction. This acceleration of the ventricular rate was accompanied by widening of the QRS complex. Using the new ventricular tachycardia criteria recently published by Brugada resulted in a diagnostic error in 7 out of the 8 cases. The recording of a wide QRS complex tachycardia in a patient on class 1 antiarrhythmic therapy for an atrial arrhythmia should alert the physician to 1/1 atrial tachycardia despite morphological electrocardiographic criteria of ventricular tachycardia. The 1/1 atrial tachycardia may be poorly tolerated and require emergency treatment. The preventive association of a drug which slows conduction through the atrioventricular node is not always effective.

Adult↗

[Non-pharmacological methods of treatment of tachycardia].

Anti-tachycardia drugs have the advantage of preventing recurrent arrhythmia in most cases but have the disadvantage of requiring long-term prescriptions and producing extra-cardiac and cardiac side effects. In addition, paradoxical arrhythmogenic effects sometimes occur. With the advent of radiofrequency catheter ablation and implantable defibrillators, a whole new range of indications for non-drug treatments suddenly became possible. Radiofrequency ablation is now a real alternative in cases of Wolff-Parkinson-White junctional tachycardia with intranodal re-entry and accessory pathways since the success rate is 95%. For atrial flutter and ventricular tachycardia, myocardial localizations of the causal lesions are more diffuse and the clinical success rate is lower. Consequently, since other arrhythmias may occur, ablative treatment is usually reserved for drug-resistant cases. An implantable defibrillator is the only treatment, with the exception of cases with an identifiable acute origin, for ventricular fibrillation. In many countries, defibrillators are also implanted for drug-resistant ventricular tachycardia.

Catheter Ablation↗