[Difficult patients in primary care: a quantitative and qualitative study]. / Pacientes de trato difícil en atención primaria: una aproximación cuantitativa y cualitativa.

AIM: To identify difficult (heartsink) patients (DP), describe their profile, and report the opinions and experiences they evoke in physicians who see them. DESIGN: Descriptive, cross-sectional study based on quantitative and qualitative methods. SETTING: Urban health care center. PARTICIPANTS: Difficult patients were selected daily from among all patients seen in six primary care practices during the period from March to May 2001. Patients were identified according to the diagnostic criteria of Ellis (patients who cause a knot in the stomach when their name appears on the list of patients with an appointment that day) and O'Dowd (patients who cause distress or discomfort). METHOD: Information was obtained on the number of DP seen, number of visits made by DP, age, sex, type of DP, level of education, occupation, family structure and comorbidity. Type of DP was determined with a modification of the Groves classification (dependent clinger, entitled demander, manipulative help-rejecter, self-destructive denier, somatizer, emotive seducer). We analyzed the opinions DP generated by examining the discourse produced during a discussion group session with 9 physicians from the participating health center and a moderator. RESULTS: A total of 82 DP were identified (prevalence.7%, i.e., 2.3% of all visits). Most (67.1%) were women. Mean age was 57.8 years (standard deviation 15.2 years). Dependent clinger patients predominated (41%). Most patients had primary-level education (62%), about one-third were retired (35%), and about one-third were married and had children (35%). Most had two or more medical diagnoses (74.4%), and many had at least one psychiatric diagnosis (40.2%).The feelings these patients evoked most often in physicians were irritability and frustration. Most physicians agreed that these patients are rare but have a severe emotional impact. Physicians believe that the skills and strategies they have to help them manage these patients are limited, and consider specific training necessary to improve them. CONCLUSIONS: Although DP are not a relevant problem in quantitative terms, they cause considerable emotional distress. Specific training in clinical interviewing is felt to be necessary given the difficulties in managing these patients.

Pacientes de trato difícil en atención primaria: una aproximación cuantitativa y cualitativa / Difficult patients in primary care: a quantitative and qualitative study

Objetivo. Identificar a los pacientes "de trato difícil" (PD), describir su perfil y las opiniones y vivencias que generan en los médicos que los atienden. Diseño. Estudio descriptivo transversal. Metodología cuantitativa-cualitativa. Emplazamiento. Centro de salud urbano. Participantes. Los PD seleccionados diariamente del total de pacientes atendidos en 6 consultas de atención primaria, entre marzo y mayo de 2001. Se identificaron mediante los criterios diagnósticos de Ellis (pacientes que provocan nudo en el estómago al leer su nombre en el listado) y O'Dowd (pacientes capaces de producir distrés, malestar).Método. Se recogió información sobre los PD visitados, número de visitas realizadas por PD, edad, sexo, clasificación, estudios, ocupación, estructura familiar y comorbilidad. Se utilizó la clasificación de Groves modificada (pasivo dependiente, exigente-agresivo, manipulador masoquista, negador-autodestructivo, somatizador, emotivo-seductor). Analizamos las opiniones que generan a partir del discurso producido en un grupo de discusión (9 médicos del centro y un moderador).Diseño. Se seleccionó a 82 pacientes (prevalencia del 0,7 por ciento [el 2,3 por ciento de las consultas realizadas]), de los que el 67,1 por ciento eran mujeres. La edad media era de 57,8 años (DE, 15,2). Predominó la paciente pasiva-dependiente (41 por ciento), con estudios primarios (62 por ciento), jubilada (35 por ciento), casada y con hijos (35 por ciento), con dos o más patologías médicas (74,4 por ciento) y al menos una psiquiátrica (40,2 por ciento).Los sentimientos que predominantemente generan en los médicos son irritabilidad y frustración. La mayoría coincide en que estos pacientes son escasos pero ocasionan un impacto emocional intenso, cree que sus habilidades y estrategias para manejarlos son limitadas y considera necesaria formación específica para mejorarlas. Conclusiones. Aunque cuantitativamente los PD no se consideran un problema relevante, provocan un gran desgaste emocional. Se consideran necesarios formación/entrenamiento específicos en entrevista clínica dadas las dificultades que presenta su manejo (AU)

Comparison of IS1245 restriction fragment length polymorphism and pulsed-field gel electrophoresis for typing clinical isolates of Mycobacterium avium subsp avium.

SETTING: Little is still known about the epidemiology and pathogenesis of Mycobacterium avium subsp avium (MASA) infection. OBJECTIVE: Examination of the reproducibility and the stability over time of pulsed-field gel electrophoresis (PFGE) and IS1245 restriction fragment length polymorphism (IS1245-RFLP) techniques. The ability of these typing systems for differentiating clinical isolates of MASA was also assessed. DESIGN: Clinical isolates recovered from 63 patients (59 human immunodeficiency virus [HIV] positive and four HIV-negative) were studied by insertion sequence IS1245 and PFGE. For the study of in vivo and in vitro stability, strains collected over time from four patients and five strains chosen at random, respectively, were used. RESULTS: The stability of PFGE and IS1245-RFLP in vitro was excellent. PFGE was also stable in vivo, but IS1245-RFLP patterns showed some variation. The discriminatory power of IS1245-RFLP and PFGE was 0.995 and 0.989, respectively. The cluster analysis did not reveal differences between strains recovered from HIV-negative and HIV-positive patients or between patients with colonisation, local infection or disseminated disease. CONCLUSION: IS1245-RFLP and PFGE are useful tools for typing MASA strains. However, IS1245 variations in vivo may complicate the analysis of epidemiological relationships.

Acquired drug resistance in Mycobacterium tuberculosis isolates recovered from compliant patients with human immunodeficiency virus-associated tuberculosis.

We describe five compliant patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB) that relapsed, with acquisition of resistance by the original Mycobacterium tuberculosis strains. Both the first and second isolates from each patient had the same IS (insertion sequence) 6110-based DNA fingerprint patterns. Three of the five patients developed TB that was resistant to rifampin alone; no mutation in the region of the rpoB gene was detected by a line probe assay in two of the isolates from these patients. We discuss several factors presumably associated with acquired drug resistance in HIV-infected patients, including exogenous reinfection, drug interactions, malabsorption of drugs, and the presence of a large organism burden.

nrdD and nrdG genes are essential for strict anaerobic growth of Escherichia coli.

In Escherichia coli ribonucleotide reduction is catalyzed by two separate enzymes during aerobic and anaerobic growth. The aerobic enzyme is coded by the nrdAB genes, the anaerobic enzyme by nrdDG. We now show that knock-out mutants of either nrdD or nrdG cannot grow during strict anaerobiosis, achieved by inclusion of sodium sulfide in the medium. Interestingly, these mutants grow well under microaerophilic conditions by overproducing the aerobic enzyme. Under such conditions wild-type bacteria turn off nrdAB and switch on nrdDG.

Construction and characterization of two lexA mutants of Salmonella typhimurium with different UV sensitivities and UV mutabilities.

Salmonella typhimurium has a SOS regulon which resembles that of Escherichia coli. recA mutants of S. typhimurium have already been isolated, but no mutations in lexA have been described yet. In this work, two different lexA mutants of S. typhimurium LT2 have been constructed on a sulA background to prevent cell death and further characterized. The lexA552 and lexA11 alleles contain an insertion of the kanamycin resistance fragment into the carboxy- and amino-terminal regions of the lexA gene, respectively. SOS induction assays indicated that both lexA mutants exhibited a LexA(Def) phenotype, although SOS genes were apparently more derepressed in the lexA11 mutant than in the lexA552 mutant. Like lexA(Def) of E. coli, both lexA mutations only moderately increased the UV survival of S. typhimurium, and the lexA552 strain was as mutable as the lexA+ strain by UV in the presence of plasmids encoding MucAB or E. coli UmuDC (UmuDCEc). In contrast, a lexA11 strain carrying any of these plasmids was nonmutable by UV. This unexpected behavior was abolished when the lexA11 mutation was complemented in trans by the lexA gene of S. typhimurium. The results of UV mutagenesis correlated well with those of survival to UV irradiation, indicating that MucAB and UmuDCEc proteins participate in the error-prone repair of UV damage in lexA552 but not in lexA11. These intriguing differences between the mutagenic responses of lexA552 and lexA11 mutants to UV irradiation are discussed, taking into account the different degrees to which the SOS response is derepressed in these mutants.

Interspecies regulation of the recA gene of gram-negative bacteria lacking an E. coli-like SOS operator.

The recA genes of Agrobacterium tumefaciens, Rhizobium meliloti, Rhizobium phaseoli and Rhodobacter sphaeroides, species belonging to the alpha-group bacteria of the Proteobacteria class, have been fused in vitro to the lacZ gene of Escherichia coli. By using a mini-Tn5 transposon derivative, each of these recA-lacZ fusions was introduced into the chromosome of each of the four species, and into that of E. coli. The recA genes of three of the alpha bacteria are induced by DNA damage when inserted in A. tumefaciens, R. phaseoli or R. meliloti chromosomes. The expression of the recA gene of R. sphaeroides is DNA damage-mediated only when present in its own chromosome; none of the genes is induced in E. coli. Likewise, the recA gene of E. coli is not induced in any of the four alpha species. These data indicate that A. tumefaciens, R. meliloti and R. phaseoli possess a LexA-like repressor, which is able to block the expression of their recA genes, as well as that of R. sphaeroides, but not the recA gene of E. coli. The LexA repressor of R. sphaeroides does not repress the recA gene of A. tumefaciens, R. meliloti, R. phaseoli or E. coli.

Analysis of the DNA damage-mediated induction of Pseudomonas putida and Pseudomonas aeruginosa lexA genes.

A fusion between the lexA gene of Pseudomonas aeruginosa and Pseudomonas putida and the lacZ gene was constructed in vitro and cloned in a mini-Tn5 transposon derivative to obtain chromosomal insertions which enable to quantitatively examine their transcriptional regulation in both Pseudomonas and E. coli. Analysis of DNA damage-mediated induction of these lexA-lacZ fusions showed that expression of P. putida and P. aeruginosa lexA genes was always higher and earlier than the expression of the lexA gene of E. coli. Furthermore, and in contrast to the lexA gene fusion of E. coli, the rates and extent of the induction of lexA gene fusion of P. putida and P. aeruginosa were largely independent of the UV doses applied. The behaviour of the lexA-lacZ fusions of two Pseudomonas species was the same regardless of whether they were inserted into their own chromosome or into E. coli.

Nucleotide sequence analysis and comparison of the lexA genes from Salmonella typhimurium, Erwinia carotovora, Pseudomonas aeruginosa and Pseudomonas putida.

The complete nucleotide sequences of the lexA genes from Salmonella typhimurium, Erwinia carotovora, Pseudomonas aeruginosa and Pseudomonas putida were determined; the DNA sequences of the lexA genes from these bacteria were 86%, 76%, 61% and 59% similar, respectively, to the Escherichia coli K12 gene. The predicted amino acid sequences of the S. typhimurium, E. carotovora and P. putida LexA proteins are 202 residues long whereas that of P. aeruginosa is 204. Two putative LexA repressor binding sites were localized upstream of each of the heterologous genes, the distance between them being 5 bp in S. typhimurium and E. carotovora, as in the lexA gene of E. coli, and 3 bp in P. putida and P. aeruginosa. The first lexA site present in the lexA operator of all five bacteria is very well conserved. However, the second lexA box is considerably more variable. The Ala-84--Gly-85 bond, at which the LexA repressor of E. coli is cleaved during the induction of the SOS response, is also found in the LexA proteins of S. typhimurium and E. carotovora. Likewise, the amino acids Ser-119 and Lys-156 are present in all of these three LexA repressors. These residues also exist in the LexA proteins of P. putida and P. aeruginosa, but they are displaced by 4 and 6 residues, respectively. Furthermore, the structure and sequence of the DNA-binding domain of the LexA repressor of E. coli are highly conserved in the S. typhimurium, E. carotovora, P. aeruginosa and P. putida LexA proteins.

One-step cloning system for isolation of bacterial lexA-like genes.

A system to isolate lexA-like genes of bacteria directly was developed. It is based upon the fact that the presence of a lexA(Def) mutation is lethal to SulA+ cells of Escherichia coli. This system is composed of a SulA- LexA(Def) HsdR- strain and a lexA-conditional killer vector (plasmid pUA165) carrying the wild-type sulA gene of E. coli and a polylinker in which foreign DNA may be inserted. By using this method, the lexA-like genes of Salmonella typhimurium, Erwinia carotovora, Pseudomonas aeruginosa, and P. putida were cloned. We also found that the LexA repressor of S. typhimurium presented the highest affinity for the SOS boxes of E. coli in vivo, whereas the LexA protein of P. aeruginosa had the lowest. Likewise, all of these LexA repressors were cleaved by the activated RecA protein of E. coli after DNA damage. Furthermore, under high-stringency conditions, the lexA gene of E. coli hybridized with the lexA genes of S. typhimurium and E. carotovora but not with those of P. aeruginosa and P. putida.