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Biomedical subjects

A Laszlo

Publications and source records attributed to A Laszlo.

At least 19 recordsLinked to original sources
PubMed2002

[Futility in geriatric medicine, a real issue].

Is futility age related? Several studies clearly demonstrate that outcome in critically ill elderly patients admitted to an intensive care unit, is more closely related to severity of illness than to age, which has little influence on prognosis. The outcome is closely associated with the severity of the illness, and age is of little influence. However, age based discrimination persists despite current recommendations from medical societies that age should not be used as a criteria for admission to intensive care. The concept of medical futility is influenced by individual or collective subjective values. Very old patients often are excluded from studies. It is difficult to apply evidence-based medicine in older people as results must be extrapolated from data in younger subjects. Thus, the true benefit of treatment is difficult to assess in the elderly. The image of the older patient, as perceived by younger health care professionals and society has a considerable impact on medical care. Medical futility is often based on clinical concepts which may lead to legal policies. It is influenced by social and economic factors. Health care professionals have a crucial role but their position, in close proximity to the patient, and its resulting emotional burden can be uncomfortable. In geriatric medicine, there is a special relationship between patients, relatives, and health professionals which requires genuine communication in order to optimise patients case. In conclusion, a balanced approach that avoids both overtreatment and therapeutic nihilism is important in order to provide old patients the best possible care.

Aged↗
PubMed2002

Quality assurance programme for drug susceptibility testing of Mycobacterium tuberculosis in the WHO/IUATLD Supranational Reference Laboratory Network: five rounds of proficiency testing, 1994-1998.

SETTING: Quality assurance for the WHO/IUATLD Global Tuberculosis Drug Resistance Surveillance Programme. OBJECTIVE: To implement an ongoing proficiency-testing programme for drug susceptibility testing (DST) of Mycobacterium tuberculosis within the WHO/IUATLD Supranational Reference Laboratories Network (SRLN). DESIGN: Five culture panels, each consisting of 10 duplicate drug-susceptible and drug-resistant clinical isolates (100 strains) of M. tuberculosis were tested for resistance to streptomycin (SM), isoniazid (INH), rifampicin (RMP) and ethambutol (EMB). DST procedures included the proportion, absolute concentration and resistance ratio methods, as well as the radiometric BACTEC 460 method. RESULTS: The efficiency, sensitivity and specificity of M. tuberculosis DST as well as the intra-laboratory reproducibility showed that the laboratories tested susceptibility to RMP and to INH very reliably, with values ranging from 97% to 99%. The testing of SM and EMB was less dependable, with values ranging from 90% to 95%. The sensitivity of testing of EMB increased from 60% in Round 1 to 98% in Round 5, without a concomitant decrease in specificity. CONCLUSIONS: This study has shown that regular proficiency testing can significantly improve the quality of DST, even in the most sophisticated TB laboratories. Mean DST efficiency levels of 92% for both SM and EMB and 97% and 99% for INH and RMP, respectively, are proposed as reasonable performance goals for the SRL network. Efficiency, consistently lower than these values, would require remedial action. Efficiency levels lower than mean -1 standard error, i.e., 80% for SM and EMB, 89% for INH and 95% for RMP, should always be considered as sub-standard performance for DST.

Antitubercular Agents↗
PubMed2001

Multiple alternative splicing forms of human RAD17 and their differential response to ionizing radiation.

In this study, we have identified four alternatively spliced RAD17 RNAs, FM1, FM2, FM3, and FM4, which are produced through alternative splicing within the first 300 base-pairs of the coding region. FM3 and FM4 are two novel forms that have not been reported before. All four alternatively spliced RAD17 RNAs were detected in the tissues we examined. However, the levels of these forms varied from tissue to tissue. The expression of these four forms was also found to differ in different phases of the cell cycle and following exposure to X-irradiation. FM2, FM1, FM4, and FM3 encode putative polypeptides consisting of 681, 670, 596, and 516 amino acids, respectively. To determine if these polypeptides were expressed in cells, we generated a polyclonal antibody using a synthetic peptide. A major band around 71 kDa and two minor bands around 73 and 62 kDa were detected in human normal fibroblasts on Western blots. These three bands appear to represent the proteins encoded by FM2 (the 73 kDa band), FM1 (the 71 kDa band), and FM4 (the 62 kDa band) since the apparent molecular weights are close to their theoretical weights of the predicted amino acid sequences. The abundance of the 71 kDa protein was not significantly affected by X-irradiation, while the abundance of the 73 and the 62 kDa proteins was increased at least 5-fold 14 h postirradiation. The differential expression of these four alternatively spliced forms in different tissues, in different phases of the cell cycle, and their differential response to X-irradiation suggest that they may perform different functions in cell-cycle regulation and in the response to irradiation.

Alternative Splicing↗
PubMed2001

Occupational transmission of Mycobacterium tuberculosis to health care workers in a university hospital in Lima, Peru.

From November 1996 through March 1997, presumptive active pulmonary tuberculosis (TB) was detected in 44 health care workers (HCWs) at a university hospital in Lima, Peru. To further assess the magnitude of the outbreak and determine risk factors for occupational Mycobacterium tuberculosis transmission, we identified HCWs in whom active pulmonary TB was diagnosed from January 1994 through January 1998, calculated rates by year and hospital work area, and conducted a tuberculin skin test (TST) survey. Thirty-six HCWs had confirmed active pulmonary TB. The rate of TB was significantly higher among the 171 HCWs employed in the laboratory than among HCWs employed in all other areas. In multivariate analysis, the only independent risk factor for HCW M. tuberculosis infection in HWCs employed in the laboratory was the use of common staff areas. Very high rates of active pulmonary TB were detected among HCWs at this hospital, and occupational acquisition in the laboratory was associated with HCW-to-HCW transmission.

Adult↗
PubMed2001

Global trends in resistance to antituberculosis drugs. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance.

BACKGROUND: Data on global trends in resistance to antituberculosis drugs are lacking. METHODS: We expanded the survey conducted by the World Health Organization and the International Union against Tuberculosis and Lung Disease to assess trends in resistance to antituberculosis drugs in countries on six continents. We obtained data using standard protocols from ongoing surveillance or from surveys of representative samples of all patients with tuberculosis. The standard sampling techniques distinguished between new and previously treated patients, and laboratory performance was checked by means of an international program of quality assurance. RESULTS: Between 1996 and 1999, patients in 58 geographic sites were surveyed; 28 sites provided data for at least two years. For patients with newly diagnosed tuberculosis, the frequency of resistance to at least one antituberculosis drug ranged from 1.7 percent in Uruguay to 36.9 percent in Estonia (median, 10.7 percent). The prevalence increased in Estonia, from 28.2 percent in 1994 to 36.9 percent in 1998 (P=0.01), and in Denmark, from 9.9 percent in 1995 to 13.1 percent in 1998 (P=0.04). The median prevalence of multidrug resistance among new cases of tuberculosis was only 1.0 percent, but the prevalence was much higherin Estonia (14.1 percent), Henan Province in China (10.8 percent), Latvia (9.0 percent), the Russian oblasts of Ivanovo (9.0 percent) and Tomsk (6.5 percent), Iran (5.0 percent), and Zhejiang Province in China (4.5 percent). There were significant decreases in multidrug resistance in France and the United States. In Estonia, the prevalence in all cases increased from 11.7 percent in 1994 to 18.1 percent in 1998 (P<0.001). CONCLUSIONS: Multidrug-resistant tuberculosis continues to be a serious problem, particularly among some countries of eastern Europe. Our survey also identified areas with a high prevalence of multidrug-resistant tuberculosis in such countries as China and Iran.

Antitubercular Agents↗
PubMed2001

[T.i.d. accelerated radiotherapy alone or alternating with chemotherapy in patients with a locally advanced ORL cancer: analysis of late toxicity].

PURPOSE: To assess late effects and quality of life in patients treated by three times daily (t.i.d.) radiotherapy with or without alternating chemotherapy for locally advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHOD: Between 1986 and 1991, 153 patients with locally advanced tumors have been included in a phase I/II study consisting of t.i.d. radiotherapy (4 h. between fractions) of 2 Gy/fraction to a total dose of 60 Gy, alternated or not with combination chemotherapy. The first group of patients received radiotherapy alone, the other group received combined modality. Ninety-two patients were eligible for late effect assessment: 61 in the combined modality group and 31 in the radiation therapy only group. The median follow-up was 45 months. All patients have been assessed according to the follow-up clinical records using the RTOG/EORTC classification. Twenty-nine patients, who were alive at the time of our study, received a questionnaire on their quality of life, and were invited for a clinical evaluation using the SOMA-LENT scale. RESULTS: Ninety percent of the patients treated by radiation therapy alone developed one or more late complications. Overall, 47% of the patients have developed severe complications (grade III and IV): 42% in the group treated by radiation therapy alone and 49% in the group treated with combined modality. In the group treated by radiation therapy alone, the most commonly damaged organs were the mucosa (83%), skin (51%) and salivary glands (42%). We observed one case of osteonecrosis and one case of radiation myelitis. In the combined modality group, 95% of patients developed one or more late sequelae, of which 79% had skin, 51% mucosa and 42% salivary gland late effects, respectively. We observed four cases of osteonecrosis. Quality of life and overall physical condition of the patients have been judged to be average by self-questionnaire. Assessment according to the SOMA-LENT scale showed serious late effects mainly at the level of the salivary glands, mandibles and teeth. Correspondence between the RTOG/EORTC and the SOMA-LENT scale was mediocre. CONCLUSION: This unconventional 4-h three times daily radiotherapy protocol resulted in very severe late effects on normal tissue. However, combination with chemotherapy resulted in minimal additional toxicity. We emphasise that the SOMA-LENT scale is neither simple to use nor easy to interpret. Quality of life is a very subjective notion and is not necessarily correlated with the objective seriousness of complications.

Chemotherapy, Adjuvant↗
PubMed2001

[Acute community acquired pneumopathy caused by Nocardia asteroides in a 93-year-old female patient].

BACKGROUND: Lower respiratory tract infection (LRTI) by Nocardia species is most often considered as an opportunistic infection occurring mainly in middle-aged adults. CASE REPORT: A 93-year old woman without any significant comorbidity other than a mild asthma, presenting with a non-resolving pneumonia, was successfully treated for a community-acquired LRTI by Nocardia asteroides. DISCUSSION: LRTI by Nocardia asteroides is a rare occurrence. Although more frequent in immuno-compromised patients (50 to 85% of cases reported), Nocardia asteroides infection also occurs in immuno-competent individuals. Very few reports describe LRTI infection by Nocardia sp. in the very old, and almost exclusively in patients with major co-morbidities or variable degrees of immuno-suppression.

Acute Disease↗
PubMed2000

Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation.

Thioredoxin (TRX) is a cytoplasmic, redox-sensitive signaling factor believed to participate in the regulation of nuclear transcription factors mediating cellular responses to environmental stress. Activation of the activator protein (AP)-1 transcription factor is thought to be mediated in part by redox-sensitive interactions between the nuclear signaling protein redox factor-1 (Ref-1) and TRX. In this study, the role of TRX and Ref-1 in the activation of the AP-1 complex was examined in HeLa and Jurkat cell lines exposed to ionizing radiation (IR). After exposure to IR, nuclear levels of immunoreactive TRX increased, accompanied by an increase in AP-1 DNA binding activity. It was shown that a physical interaction between Ref-1 and TRX occurs within the nucleus and is enhanced after exposure to IR. Furthermore, TRX immunoprecipitated from irradiated cells was capable of activating AP-1 DNA binding activity in nonirradiated nuclear extracts. In addition, immunodepletion of Ref-1 from nuclear extracts demonstrated that the increase in AP-1 DNA binding activity after IR was also dependent upon the presence of Ref-1 from irradiated cells. Finally, the ability of both TRX and Ref-1 from irradiated cells to stimulate AP-1 DNA binding in nonirradiated nuclear extracts was abolished by chemical oxidation and restored by chemical reduction. These results indicate that, in response to IR, TRX and Ref-1 undergo changes in redox state that contribute to the activation of AP-1 DNA binding activity. These experiments suggest that a redox-sensitive signaling pathway leading from TRX to Ref-1 to the AP-1 complex participates in the up-regulation of DNA binding activity in response to ionizing radiation.

Animals↗
PubMed2000

Metabolism of carnitine in phenylacetic acid-treated rats and in patients with phenylketonuria.

The effect of metabolites accumulating in phenylketonuria (PKU) was investigated on carnitine metabolism in rats and in patients with PKU. Of phenylacetic acid (PEAA), phenylpyruvic acid and homogentisic acid the PEAA was found to be the most effective in inhibiting carnitine biosynthesis in rats. Following 60 min, a single intraperitoneal dose of PEAA the relative conversion rate, i. e. the hydroxylation, of tracer [Me-(3)H]butyrobetaine to [Me-(3)H]carnitine decreased from 62.2+/-6.00% to 39.4+/-5.11% (means+/-S.E.M., P<0.01) in the liver, in the only organ doing this conversion in rats. The conversion of loading amount of unlabeled butyrobetaine to carnitine was also markedly reduced. The impaired hydroxylation of butyrobetaine was reflected by a reduced free and total carnitine levels in the liver and a reduced total carnitine concentration in the plasma. PEAA decreased the hepatic level of glutamic acid and alpha-ketoglutaric acid (alpha-KG), suggesting a mechanism for the reduced flux through the butyrobetaine hydroxylase enzyme, because alpha-KG is an obligatory co-enzyme. In the plasma and urine of PKU patients on unrestricted diet, markedly decreased total carnitine levels were detected. In the liver of PEAA-treated rats and urine of PKU patients, a novel carnitine derivative, phenacetyl-carnitine was verified by HPLC and gas chromatography-mass spectrometry.

Adult↗
PubMed1999

Hsc40, a new member of the hsp40 family, exhibits similar expression profile to that of hsc70 in mammalian cells.

Here, we report the identification and characterization of a new hsp40 family member, heat shock cognate 40 (hsc40), which may be a specific functional partner for hsc70. The hsc40 gene consists of five exons and four introns. The previously characterized hsp40 gene contains only three exons and two introns. Despite this difference in the numbers of exons and introns, the structures of these two genes are actually quite similar. If the first two exons and introns of the hsc40 gene are excluded, the rest is essentially the same as the whole hsp40 gene. The intron/exon boundaries of the hsc40 and hsp40 genes are conserved with respect to amino acid coding, indicating that the hsp40 gene might have arisen from a duplicated hsc40 gene, which developed a new transcription-regulatory mechanism in the second intron. Hsc40 is evolutionally conserved. There is over 95% sequence identity between the putative mouse and human hsc40 proteins. However, there is only 60% sequence identity between the hsc40 and hsp40 proteins from either human or mouse cells. Northern blot analysis of various tissues and cells in culture revealed that this gene was expressed under normal conditions, and its expression was further increased after various stress treatments. The expression pattern of the hsc40 gene is very similar to that of the hsc70 gene under both normal and stress conditions, whereas the hsp40 gene exhibited an expression pattern more similar to that of hsp70 genes on the same Northern blots. These results, considered along with the high rate of sequence conservation between the same proteins from different species and high rate of variation between the two different proteins from the same species, strongly suggest that hsc40 and hsp40 may perform different functions and/or have different specificities in the cell.

3T3 Cells↗
PubMed1999

Unique features of Chinese hamster S13 gene relative to its human and Xenopus analogs.

We have cloned and sequenced the ribosomal protein S13 gene from the Chinese hamster fibroblast HA-1 cells. The predicted protein encoded by this gene is identical to the human ribosomal protein S13, except for one amino acid substitution at residue 29, which is an alanine in the hamster protein and a threonine in that of humans. The physical organization of the six exons and five introns in the hamster S13 gene is also identical to that found in the human and Xenopus genes with respect to the amino acid codes, even though there are small differences in the lengths of the introns. The striking feature is that unlike its human and Xenopus counterparts, which encode two U14 snoRNAs in two separate introns, the hamster S13 gene encodes no U14 snoRNA. Instead, the hamster gene has a pseudo-U14 coding sequence in its third intron. Our data support the idea that the single copy of the hsc70/U14 gene, which we had previously characterized, is the only source for the production of both U14 snoRNA and hsc70 mRNA species in hamster HA-1 cells.

Amino Acid Sequence↗
PubMed1999

The risk of acute major upper gastrointestinal bleeding among users of aspirin and ibuprofen at various levels of alcohol consumption.

OBJECTIVE: Major upper gastrointestinal bleeding (UGIB) is the most important adverse effect of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). Alcoholic beverages also precipitate UGIB. This analysis was conducted to evaluate whether the deleterious effects of NSAIDs are further increased among drinkers. METHODS: An interview-based, case-control study was conducted in the U.S. and Sweden; 1224 patients hospitalized with acute major UGIB due to newly occurring peptic ulcer or gastritis were compared to 2945 neighbor controls. RESULTS: Compared with those who drank less than one drink/wk, the relative risk of acute UGIB increased with increasing alcohol consumption, rising to 2.8 among those who drank > or = 21 drinks/wk. Among current drinkers, the relative risk of acute UGIB due to the use of aspirin was raised at all levels of alcohol consumption; the estimate for aspirin taken at least every other day (regular use) at doses of > 325 mg among all current drinkers combined was 7.0; for regular use at lower doses, the corresponding estimate was 2.8, and for any occasional use, it was 2.4. All estimates were statistically significant. Data for ibuprofen were more limited, but the relative risk estimates did not appear to vary consistently with level of alcohol consumption. For regular use (all doses combined), the estimate among all drinkers combined was significantly elevated, at 2.7; occasional ibuprofen use was not associated with UGIB (1.2). There were insufficient data to evaluate other NSAIDs according to alcohol consumption. CONCLUSIONS: The findings suggest that acute UGIB is similarly associated with the use of the two most common nonprescription NSAIDs, aspirin and ibuprofen, at all levels of alcohol consumption. As heavy alcohol intake independently increases the risk, the incidence of UGIB is highest among persons who are both heavy drinkers and users of aspirin or ibuprofen.

Acute Disease↗