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Biomedical subjects

H Klein

Publications and source records attributed to H Klein.

At least 91 records · Page 5Linked to original sources
PubMed1997

Problems and pitfalls in evaluating studies for pacing in heart failure.

Pacing therapy has been recently proposed as a new non-pharmacological approach to patients suffering from congestive heart failure refractory to medical therapy (refractory CHF), but the extention and the real benefit of this method remains to be defined. Although pacing therapy for refractory CHF has been restricted to patients in sinus rhythm presenting atrial, atrioventricular or interventricular conduction disturbances, considerable conflicting results have been published. The contradictory data is most likely due to large heterogeneity of the investigated study population (ie etiology of CHF, NYHA class, duration of follow-up, end-points of the study, etc.), to difference in study methology as well as in the site and modality of acute and chronic pacing. Although several empirical data indicates, at least in some individuals, major improvement in CHF symptoms by properly coordinating the atria and the ventricles thus reducing pre-systolic mitral and/or tricuspidal regurgitation or finally, prolonging the diastolic filling time, a lack of understanding of the mechanisms responsible for acute and chronic benefit persists. In evaluating pacemaker therapy as a new supportive treatment for CHF, the clinical investigator must consider that each study protocol embodies assumptions and methodological limitations and thus provides an incomplete analysis of potential benefit. Relying solely on noninvasive measures is risky due to problems of sensitivity and repeatability.

Cardiac Pacing, Artificial↗
PubMed1997

Hamster ribosomal protein S24 multigene family: genomic organization and molecular structure of two pseudogenes.

A cDNA coding for the hamster S24 ribosomal protein was used to isolate homologous genes from a Syrian hamster fibroblast genomic library. Southern analysis, using S24 ribosomal protein cDNA and two probes derived from the 5' and 3' ends, suggests that the S24 ribosomal protein family is composed of at least 3 related members in the hamster genome, and of 6-10 members in the mouse genome. I describe the isolation of nine independent lambda recombinant phages that altogether carry two different genes encoding S24 ribosomal proteins. Sequence analysis indicates that each of these two genes contain sequences related to the S24 ribosomal protein but lack introns and differ in their flanking sequences. On the basis of these features, I propose that these two genes are processed pseudogenes. Interestingly, one of them is flanked by two different repetitive sequences, homologous to satellite DNA, whose functions are unknown. I also show that in the hamster genome the S24 ribosomal protein mRNA is transcribed from a unique gene using a precise initiation site.

Aniline Compounds↗
PubMed1997

Gait analysis of the hemophilic ankle with silicone heel cushion.

Shock absorption becomes very important in damaged joints with destroyed cartilage and progressive muscular imbalance as occurs in hemarthropathy. The effects of silicone heel cushioning on the ankle motion of hemophilic patients in different stages of hemarthropathy of the ankle joints was measured using an ultrasound motion analysis system. It is concluded that silicone heel cushioning has no influence on ankles in the late stage of hemarthropathy. Silicone heel cushioning will lead to uncontrolled changes of the ankle joint in the early hemarthropathic ankle, involving the tibiotalar and the subtalar joints. The angular velocity of the ankle is increased producing higher acceleration at the ankle joint. The higher angle acceleration is related to higher joint loading uncontrolled by the muscles. The resulting uncoordinated motion can cause ligamentous overloading, strains, and a higher probability of joint bleeding. Therefore, silicone heel cushioning or other shock absorbing devices that return the energy immediately to the foot are not useful for prevention and treatment of chronic hemophilic synovitis and may cause additional deterioration of the joint.

Acceleration↗
PubMed1996

Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators.

BACKGROUND: Unsustained ventricular tachycardia in patients with previous myocardial infarction and left ventricular dysfunction is associated with a two-year mortality rate of about 30 percent. We studied whether prophylactic therapy with an implanted cardioverter-defibrillator, as compared with conventional medical therapy, would improve survival in this high-risk group of patients. METHODS: Over the course of five years, 196 patients in New York Heart Association functional class I, II, or III with prior myocardial infarction; a left ventricular ejection fraction < or = 0.35; a documented episode of asymptomatic unsustained ventricular tachycardia; and inducible, nonsuppressible ventricular tachyarrhythmia on electrophysiologic study were randomly assigned to receive an implanted defibrillator (n = 95) or conventional medical therapy (n=101). We used a two-sided sequential design with death from any cause as the end point. RESULTS: The base-line characteristics of the two treatment groups were similar. During an average follow-up of 27 months, there were 15 deaths in the defibrillator group (11 from cardiac causes) and 39 deaths in the conventional-therapy group (27 from cardiac causes) (hazard ratio for overall mortality, 0.46; 95 percent confidence interval, 0.26 to 0.82; P=0.009). There was no evidence that amiodarone, beta-blockers, or any other antiarrhythmic therapy had a significant influence on the observed hazard ratio. CONCLUSIONS: In patients with a prior myocardial infarction who are at high risk for ventricular tachyarrhythmia, prophylactic therapy with an implanted defibrillator leads to improved survival as compared with conventional medical therapy.

Adult↗
PubMed1996

Coarsening Due to Thermally Induced Marangoni Convection

The growth of closely packed droplets in a decomposing butoxyethanol/water mixture is studied at reduced gravity during scaled times t* = t(D/xi2) on the order of t* = 10(6) (t, time; D, diffusion coefficient; xi, correlation length). Thermally induced Marangoni convection at the surfaces of the droplets causes an enhancement of the coarsening process.

Journal Article↗
PubMed1996

Clinical relevance of stored electrograms for implantable cardioverter-defibrillator (ICD) troubleshooting and understanding of mechanisms for ventricular tachyarrhythmias.

A major problem in patients with cardioverter-defibrillators is to determine reliably the mechanism for spontaneous implantable cardioverter-defibrillator (ICD) discharges. Electrogram storage in ICD devices is comparable to that in permanent Holter monitors. Stored bipolar electrograms obtained from the sensing or shocking lead system contain a wide variety of different information. Intracardiac electrograms (EGMs) recorded from pace/sense electrodes (or "near-field" EGMs) show bipolar signals that have a distinct absence of any atrial activity during ventricular tachycardia or sinus rhythm. In contrast, the EGMs recording from the shocking electrodes, integrating a much larger area of myocardium, provide a more global visualization of electrical activity, which includes both atrial and ventricular deflections. Improved diagnostic capabilities available in the new generation ICD devices, in particular the stored intracardiac EGMs, facilitate sensing error diagnosis, permit a better evaluation of device function and ICD detection algorithms, and are helpful for reprogramming in order to overcome or prevent errors. In addition, EGMs give us a unique opportunity to gather information about the arrhythmic mechanism of the sudden cardiac death syndrome. Information such as the day and time of the episode, the preceding heart rate, the influence of the coupling interval of preceding premature beats, and their morphology can be gained from the analysis of stored EGM recordings. Although the availability of stored intracardiac EGMs are of enormous value in troubleshooting of ICD problems, they are occasionally not conclusive and must be complemented by additional techniques in order to complete the diagnosis. The information obtained by the analysis of stored intracardiac EGMs together with a database of EGMs can be of great importance for further improvements in future devices and may provide insights as to which patients are likely to benefit most from ICD therapy.

Defibrillators, Implantable↗
PubMed1996

Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications.

BACKGROUND: Rheumatoid arthritis is a common disease that causes substantial morbidity and mortality. The responses of patients with rheumatoid arthritis to treatment with a single so-called disease-modifying drug, such as methotrexate, are often suboptimal. Despite limited data, many patients are treated with combinations of these drugs. METHODS: We enrolled 102 patients with rheumatoid arthritis and poor responses to at least one disease-modifying drug in a two-year, double-blind, randomized study of treatment with methotrexate alone (7.5 to 17.5 mg per week), the combination of sulfasalazine (500 mg twice daily) and hydroxychloroquine (200 mg twice daily), or all three drugs. The dose of methotrexate was adjusted in an attempt to achieve remission in all patients. The primary and point of the study was the successful completion of two years of treatment with 50 percent improvement in composite symptoms of arthritis and no evidence of drug toxicity. RESULTS: Fifty of the 102 patients had 50 percent improvement at nine months and maintained at least that degree of improvement for two years without evidence of major drug toxicity. Among them were 24 of 31 patients treated with all three drugs (77 percent), 12 of 36 patients treated with methotrexate alone (33 percent, P < 0.001 for the comparison with the three-drug group), and 14 of 35 patients treated with sulfasalazine and hydroxychloroquine (40 percent), P = 0.003 for the comparison with the three-drug group). Seven patients in the methotrexate group and three patients in each of the other two groups discontinued treatment because of drug toxicity. CONCLUSIONS: In patients with rheumatoid arthritis, combination therapy with methotrexate, sulfasalazine, and hydroxychloroquine is more effective than either methotrexate alone or a combination of sulfasalazine, and hydroxychloroquine.

Adult↗
PubMed1996

Characterization of genomic clones encoding two microneme antigens of Sarcocystis muris (Apicomplexa).

Subgenomic libraries were constructed from Sarcocystis muris total DNA. Hybridization screening with a microneme-specific cDNA probe resulted in two clones that were sequenced. The amino acid sequences deduced showed 87% homology among each other. Three different domains were recognized within both polypeptides. Domain I includes the putative N-terminal signal sequence. Domain II represents a strongly hydrophilic region, entirely homologous in the two genes. Domain III encodes the mature polypeptides with theoretical molecular masses of 15.1 kDa each. Among 28 amino acid changes in this region, 19 replacements are conservative. The putative polypeptides carried 12 conserved cysteine residues and showed homologies with plasma kallikrein, factor XI, and an antigen of Eimeria tenella. The recombinant proteins are recognized by the monoclonal antibody 3A8 directed against the 16/17-kDa microneme antigen of S. muris cystozoites. Antiserum raised against one of the purified fusion proteins cross-reacts with its counterpart and with the native 16/17-kDa band-doublet.

Amino Acid Sequence↗
PubMed1996

In vitro biosynthesis and in vivo processing of the major microneme antigen of Sarcocystis muris cyst merozoites.

The cDNA clone pSM/1.6 encoding the 26.5-kDa precursor molecule of the 16/17-kDa microneme antigen of Sarcocystis muris cyst merozoites was expressed in a cell-free translation/translocation system to study translocation of the protein across membranes. The antigen was found to be translocated across heterologous endoplasmic reticulum membranes. Translocation was accompanied by cleavage of a signal peptide to create a 23-kDa polypeptide that was completely protected from digestion with proteinase K. Pulse-chase analysis of [35S]-methionine-labeled S. muris cyst merozoites demonstrated that the 16/17-kDa antigen derived from a 23-kDa precursor molecule and that its processing occurred at between a few minutes and 2 h after biosynthesis. This leads to the conclusion that the native microneme antigen is secreted from the parasite cell via the endoplasmic reticulum. Sorting into micronemes might occur during transition through a Golgi-like structure, involving cleavage of the hydrophilic propeptide to create the mature 16/17-kDa protein.

Animals↗
PubMed1995

T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years.

In 1990, a clinical trial was started using retroviral-mediated transfer of the adenosine deaminase (ADA) gene into the T cells of two children with severe combined immunodeficiency (ADA- SCID). The number of blood T cells normalized as did many cellular and humoral immune responses. Gene treatment ended after 2 years, but integrated vector and ADA gene expression in T cells persisted. Although many components remain to be perfected, it is concluded here that gene therapy can be a safe and effective addition to treatment for some patients with this severe immunodeficiency disease.

Adenosine Deaminase↗
PubMed1995

Nemaline myopathy: two autopsy reports.

Nemaline myopathy belongs to the group of congenital non-progressive myopathies; however, in rare cases death occurs in early infancy. We report two cases of rapidly fatal nemaline myopathy. The first patient, who died at the age of 26 months, showed atrophy of type 1 fibers containing numerous rods in biopsy sections. Biopsy of the second patient, who had died at the age of 5 months, revealed severe maturational arrest and myopathy, but rods were so rare that diagnosis could only be made at the ultrastructural level. Autopsy of both patients showed that atrophy of type 1 fibers and maturational arrest had disappeared in the very same muscles; rods had moved to a central position in the first and significantly increased in number in the second case. Diaphragma muscles contained abundant amounts of rods in both cases. The cardiac musculature showed a few rods only in the first patient, who had developed heart insufficiency 11 months prior to death. Immunohistochemical analysis showed that rods did not contain desmin or ubiquitin.

Biopsy↗
PubMed1995

Effects of angiotensin II and phenylephrine on urinary endothelin in normal female volunteers.

Endothelin (ET) is a 21-amino acid peptide produced and secreted mainly by endothelial cells. Small amounts of ET are found in plasma, whereas large amounts are present in the urine. Despite the abundance of ET in the kidneys and urine, little is known about its regulation and clinical significance. The present study was designed to examine the effects of angiotensin II (Ang II) and phenylephrine (Phe) on the excretion of ET in normal female volunteers. Ang II and Phe were infused for 1 hour each and titrated to increase the mean arterial pressure by 20 mm Hg. There was a 60-minute recovery period before the second drug, and the order of the drugs was randomized. Infusion of Phe induced mild diuresis and natriuresis, which were associated with a significant increase in the excretion of ET. In addition, Phe significantly increased plasma atrial natriuretic factor (ANF). In contrast, infusion of equipressor doses of Ang II decreased urinary sodium excretion and did not significantly alter the excretion of ET. Moreover, Ang II induced only a small and nonsignificant increase in plasma ANF. These results demonstrate that (1) physiological doses of Ang II do not affect excretion of either ET or ANF; (2) Phe markedly increased the excretion of ET and ANF, independently of its effect on blood pressure; and (3) neither agent changed plasma ET, but Phe increased plasma ANF.

Adolescent↗
PubMed1995

Site selection for Mars exobiology.

The selection of sites on Mars that have a high priority for exobiological research is fundamental for planning future exploration. The most immediate need is to identify targets for high resolution orbital imaging during the Mars Observer and Mars '94/'96 missions that can be used to refine site priorities for surface exploration. We present an objective approach to site selection whereby individual sites are selected and scored, based on the presence of key geological features which indicate high priority environments. Prime sites are those that show evidence for the prolonged activity of liquid water and which have sedimentary deposits that are likely to have accumulated in environments favorable for life. High priority areas include fluvio-lacustrine (stream-fed lake systems), springs, and periglacial environments. Sites where mineralization may have occurred in the presence of organisms (e.g. springs) are given high priority in the search for a fossil record on Mars. A systematic review of Viking data for 83 sites in the Mars Landing Site Catalog resulted in the selection of 13 as being of exobiological interest. The descriptions of these sites were expanded to address exobiological concerns. An additional five sites were identified for inclusion in the second edition of the MLSC. We plan to broaden our site selection activities to include a systematic global reconnaissance of Mars using Viking data, and will continue to refine site priorities for exobiological research based on data from future missions in order to define strategies for surface exploration.

Exobiology↗