Comparative assessment of Vibrio virulence in marine fish larvae.

Vibrionaceae infections are a major obstacle for marine larviculture; however, little is known about virulence differences of Vibrio strains. The virulence of Vibrio strains, mostly isolated from vibriosis outbreaks in farmed fish, was tested in larval challenge trials with cod (Gadus morhua), turbot (Scophthalmus maximus) and halibut (Hippoglossus hippoglossus) using a multiwell dish assays with single-egg/larvae cultures. The strains differed significantly in virulence as some caused a high mortality of larva reaching 100% mortality after a few days, while others had no or only marginal effects on survival. Some Vibrio strains were pathogenic in all of the larva species, while some caused disease only in one of the species. Twenty-nine of the Vibrio anguillarum strains increased the mortality of larvae from at least one fish species; however, pathogenicity of the strains differed markedly. Other Vibrio species had no or less pronounced effects on larval mortalities. Iron uptake has been related to V. anguillarum virulence; however, the presence or absence of the plasmid pJM1 encoding anguibactin did not correlate with virulence. The genomes of V. anguillarum were compared (D. Castillo, P.W. D'Alvise, M. Middelboe & L. Gram, unpublished data) and most of the high-virulent strains had acquired virulence genes from other pathogenic Vibrio.

The latent structure of the functional dyspepsia symptom complex: a taxometric analysis.

OBJECTIVES: Rome III introduced a subdivision of functional dyspepsia (FD) into postprandial distress syndrome and epigastric pain syndrome, characterized by early satiation/postprandial fullness, and epigastric pain/burning, respectively. However, evidence on their degree of overlap is mixed. We aimed to investigate the latent structure of FD to test whether distinguishable symptom-based subgroups exist. METHODS: Consecutive tertiary care Rome II FD patients completed the dyspepsia symptom severity scale. Confirmatory factor analysis (CFA) was used to compare the fit of a single factor model, a correlated three-factor model based on Rome III subgroups and a bifactor model consisting of a general FD factor and orthogonal subgroup factors. Taxometric analyses were subsequently used to investigate the latent structure of FD. KEY RESULTS: Nine hundred and fifty-seven FD patients (71.1% women, age 41 ± 14.8) participated. In CFA, the bifactor model yielded a significantly better fit than the two other models (χ² difference tests both p < 0.001). All symptoms had significant loadings on both the general and the subgroup-specific factors (all p < 0.05). Somatization was associated with the general (r = 0.72, p < 0.01), but not the subgroup-specific factors (all r < 0.13, p > 0.05). Taxometric analyses supported a dimensional structure of FD (all CCFI<0.38). CONCLUSIONS AND INFERENCES: We found a dimensional rather than categorical latent structure of the FD symptom complex in tertiary care. A combination of a general dyspepsia symptom reporting factor, which was associated with somatization, and symptom-specific factors reflecting the Rome III subdivision fitted the data best. This has implications for classification, pathophysiology, and treatment of FD.

Luminal uptake of Vibrio (Listonella) anguillarum by shed enterocytes--a novel early defence strategy in larval fish.

As adhesion and translocation through fish gut enterocytes of the pathogen Vibrio (Listonella) anguillarum are not well investigated, the effective cause of disease and mortality outbreaks in larval sea bass, Dicentrarchus labrax, suffering from vibriosis is unknown. We detected V. anguillarum within the gut of experimentally infected gnotobiotic sea bass larvae using transmission electron microscopy and immunogold labelling. Intact bacteria were observed in close contact with the apical brush border in the gut lumen. Enterocytes contained lysosomes positive for protein A-gold particles suggesting intracellular elimination of bacterial fragments. Shed intestinal cells were regularly visualized in the gut lumen in late stages of exposure. Some of the luminal cells showed invagination and putative engulfment of bacterial structures by pseudopod-like formations. The engulfed structures were positive for protein A-colloidal gold indicating that these structures were V. anguillarum. Immunogold positive thread-like structures secreted by V. anguillarum suggested the presence of outer membrane vesicles (MVs) hypothesizing that MVs are potent transporters of active virulence factors to sea bass gut cells suggestive for a substantial role in biofilm formation and pathogenesis. We put forward the hypothesis that MVs are important in the pathogenesis of V. anguillarum in sea bass larvae.

An aerolysin-like enterotoxin from Vibrio splendidus may be involved in intestinal tract damage and mortalities in turbot, Scophthalmus maximus (L.), and cod, Gadus morhua L., larvae.

Vibrio splendidus is a pathogen that can cause major losses during the early stages of larval turbot rearing when live feed (rotifers or Artemia) is used. As haemolytic bacteria have often been associated with larval rearing losses, we studied the role of the V. splendidus haemolysin in infection of larvae. From a bank of over 10,000 transposon mutants of V. splendidus, two different types of haemolysin-negative mutants were obtained. Both had lost virulence for larval fish, and immunohistochemistry showed that the transposon mutant studied colonized the turbot larval intestinal tract at a similar level to the wild-type organism but did not cause damage or signs of enteritis found with the wild-type organism. One transposon insertion site was located within a gene with high homology to aerolysin, the cytolytic toxin produced by several Aeromonas spp. The haemolysin, which we have termed vibrioaerolysin, had properties similar to aerolysin and osmotic protection studies showed that it formed pores in the membranes of erythrocytes of similar diameter to those of aerolysin. The Tn10 insertion site of the second transposon mutant was in an adjacent ToxR-like gene, suggesting that this might control expression of the vibrioaerolysin. The gastroenteritis caused by Aeromonas spp. in humans is considered to be due to production of aerolysin causing cyclic AMP-dependent chloride secretion in cells of the gastrointestinal tract. Damage to the intestinal tract of marine fish larvae could occur in a similar way, and it is possible that several Vibrio spp. found in the developing bacterial flora of the larval fish gut can secrete aerolysin-like toxins leading to death of larvae in the early rearing stages. Routine bacteriological screening on blood agar plates of live feed is recommended with measures to reduce the concentrations of haemolytic bacteria in rearing systems.

Treating primary insomnia: clinical effectiveness and predictors of outcomes on sleep, daytime function and health-related quality of life.

Primary insomnia, as defined by DSM-IV-TR, refers to a persistent sleep disturbance which is not connected to a current psychiatric or physical condition, but significantly impairs social and occupational functioning. This study explored the impact of Cognitive Behavioral Therapy for Insomnia (CBT-i) on sleep, daytime functioning and health-related quality of life (HRQoL). Next, we investigated which factors predicted positive treatment outcome by examining demographics, insomnia characteristics, baseline levels of daytime function, HRQoL, sleep-disruptive beliefs and psychological health on post-treatment sleep quality, daytime function and HRQoL. 138 consecutive primary insomnia patients completed questionnaires pre- and post-treatment and at 6 months follow-up. After CBT-i, robust clinical improvements were observed in sleep, daytime function and HRQoL, regardless of age, gender, type or duration of the complaint. Patients with pre-treatment severe insomnia, pronounced daytime impairment and low psychological well-being benefited most.

Novel application of nitrifying bacterial consortia to ease ammonia toxicity in ornamental fish transport units: trials with zebrafish.

AIMS: To evaluate whether two commercial nitrifying bacterial consortia can function as biocontrol agents in ornamental fish transporting systems. METHODS AND RESULTS: The consortia were applied in a simulated set-up using zebrafish as the model organism in three trials. The efficacy of the bacterial consortia in controlling the ammonia level was validated by measuring water quality parameters such as total ammonia, nitrate and pH of the transport water. The bacterial community structure in the transport unit was studied using denaturing gradient gel electrophoresis. The consortia tested improved the nitrifying activity that in turn facilitated the reduction of ammonia that had accumulated during the transport. Bacterial profiles revealed the presence of both ammonia-oxidizing and nitrite-oxidizing bacteria in the transport bags. CONCLUSIONS: The application of the consortia during the transportation of zebrafish could profoundly improve the water quality by curbing ammonia accumulation. SIGNIFICANCE AND IMPACT OF THE STUDY: The potential of applying nitrifying bacteria as a bioremediation practice during the transport of ornamental fish has been demonstrated and this innovative approach contributes to the amelioration of current fish welfare in ornamental fish trade.

Effects of a shortened asthma self-management group program.

OBJECTIVE: Asthma self-management programs are effective but often time-consuming.We evaluated the effects of a shortened asthma self-management program on asthma knowledge, morbidity and asthma-related behaviour in a group of moderate to severe adult asthmatics. METHODS: The effects of the program were evaluated with a one year prospective trial in a group of 55 asthmatics (mean age 45 yrs, 42% males, N=26 in intervention group, N=29 in control group) by administering questionnaires and diary exercises at baseline, immediately, 3 and 12 months after the end of the program. RESULTS: Asthma-related knowledge and hyperventilation symptoms improved more in the intervention than in the control group and this effect was maintained until 3 months after participation. General asthma symptoms improved significantly, but substantial symptom improvements were also found in the control group. The original effects in the intervention group persisted partly but not significantly 1 year after participation. No significant effects were found on pulmonary function. CONCLUSIONS: Based on our preliminary results, we conclude that our shortened asthma self-management program had an impact on knowledge and asthma symptoms, especially hyperventilation symptoms, until 3 months after the end of the program. Continuous reinforcement and specifying the program content are essential aspects to obtain more robust and long-lasting effects when administering shortened asthma self-management programs.

[Cognitive-behavioural therapy for primary insomnia: effectiveness in a clinical setting]. / Cognitieve gedragstherapie voor primaire insomnia: effectiviteit in een klinische setting.

BACKGROUND: The effectiveness of cognitive behavioural therapy for insomnia (cbt-i) has been demonstrated in randomised controlled trials (rct's) with primary insomnia patients and, more recently, with comorbid insomnia patients. The clinical impact of the treatment is mainly on sleep quality and the use of medication and to a lesser extent on daytime functioning. So far there have been very few studies of the effectiveness of cbt-i in clinical settings. AIM: To examine the effectiveness of cbt-i for primary insomnia via an uncontrolled prospective study in a clinical tertiary care setting. METHOD: We included 76 patients with primary insomnia, most of whom having been referred by their gp or medical specialist to the Leuven University Centre of Sleep, who followed a 6-week course of cbt-i as a group. Effects of cbt-i on primary and secondary outcome measures were studied. results cbt-i resulted in a significant improvement in all primary sleep variables such as sleep onset, sleep efficiency and sleep quality. The increase in total sleep time was less substantial, probably as a result of the specific sleep restriction guidelines. There was also a significant improvement on several secondary parameters, in particular dysfunctional cognitions, affective state, general health and use of medication. CONCLUSIONS: cbt-i has a significant impact on sleep quality, medication use and daytime functioning in primary insomniacs in a clinical tertiary care setting.

Occurrence of Francisella piscicida in farmed and wild Atlantic cod, Gadus morhua L., in Norway.

Francisellosis, caused by the bacterium Francisella piscicida, has become one of the most serious diseases in Atlantic cod production in Norway. The major aim of this study was to determine the distribution of F. piscicida in farmed and wild fish in areas with cod farming along the Norwegian coast, and its occurrence in cod from areas without cod farming. Two real-time PCR assays, targeting the 16S rRNA gene and the FopA gene of F. piscicida, were developed since sensitive and specific diagnostic tools are required for detecting asymptomatic carriers of the bacterium. A total of 422 wild cod from 13 sampling areas and 955 farmed cod from 10 areas along the coast of Norway were examined. Using the real-time polymerase chain reaction (PCR) assays, F. piscicida was detected in wild populations of cod from all counties examined south of Sogn og Fjordane in southern Norway (overall prevalence 13%, n = 221). Wild cod north of Sogn og Fjordane were negative for the bacterium (n = 201). Farmed cod from most parts of Norway were F. piscicida positive. The apparent absence of the bacterium in wild populations of cod in the northern parts of Norway and its widespread occurrence in wild cod from southern parts of Norway is believed to relate to differences in seawater temperatures.

Complicaciones postoperatorias de la serie prospectiva de pacientes con hernioplastia inguinal, en protocolo de hospitalización acortada del Hospital Dr. Gustavo Fricke de Viña del Mar / Complications of inguinal hernia repair

La hernioplastia es la técnica quirúrgica más comúnmente realizada por el cirujano general. Desde la década de los 80, existe un auge por la cirugía ambulatoria en esta patología. Objetivo: Evaluar la incidencia de complicaciones postoperatorias y posibles asociaciones con factores de riesgo, en hernioplastia inguinal electiva en protocolo de hospitalización abreviada. Material y Método: Serie de casos prospectiva de 214 pacientes operados de hernia inguinal, entre abril del 2003 y noviembre del 2005. Se excluyeron los pacientes con ASA III y IV. El análisis estadístico fue realizado mediante la prueba de Chi cuadrado (univariables), y regresión logística (multivariables), SPSS 11.0. p <0,05. Resultados: El promedio de edad fue de 54,3 años (17-84), predominio masculino (90,7 por ciento). Se controló al 100 por ciento de los casos en los primeros 30 días de la intervención, control telefónico (78 por ciento), y en el policlínico (100 por ciento). Complicaciones postoperatorias presentaron el 14,9 por ciento de los casos, la más frecuente fue el seroma (4,2 por ciento), la más grave atrofia testicular y dolor crónico invalidante en 1 paciente (0,47 por ciento), debiendo finalmente realizar orquiectomía. Infección de herida operatoria correspondió al 0,47 por ciento, un paciente ASA I. Los menores de 65 años tuvieron un riesgo relativo de 2,31 de presentar complicaciones. El nivel de satisfacción usuaria fue bueno. El 90 por ciento ha sido controlado hasta agosto del 2006, media de seguimiento de 24 meses y sin presentar recidiva. Conclusiones: La herniorrafia inguinal con hospitalización abreviada, en el hospital Dr. Gustavo Fricke de Viña del Mar, tiene significativamente mayores complicaciones en los menores de 65 años. También ha logrado niveles de satisfacción adecuados, con un mínimo de complicaciones postoperatorias inmediatas.

Background: Hernia repair in adults is the most commonly performed surgical procedure by general surgeons. Aim: To evaluate the incidence of postoperative complications in elective inguinal hernioplasty with abbreviated hospital stay. Material and Methods: Prospective series of 214 patients aged 16 to 84 years (194 males), operated for inguinal hernia between April 2003 and November 2005. Patients classified as American Society of Anesthesiologists (ASA) III or IV were excluded from the study. Results: All patients were followed during the first 30 days after surgery by telephone and control at the outpatient clinic. Fifteen percent had complications. The most common was seroma in 4 percent and the most serious was a testicular atrophy and chronic invalidating pain in one patient, that required an orchidectomy. One patient had a surgical wound infection. Patients of less than 65 years had an odds ratio of 2.13 for complications, when compared with their older counterparts. The level of client satisfaction was good. After 24 months of follow up 90 percent of patients were under control and without relapse. Conclusions: Inguinal hernia repair with abbreviated hospital stay has a low incidence of complications.

Treating experimentally induced vibriosis (Listonella anguillarum) in cod, Gadus morhua L., with florfenicol.

This study was performed to determine the efficacy of orally administered florfenicol in the treatment of experimentally induced vibriosis (Listonella anguillarum) in cod, Gadus morhua. The L. anguillarum strain HI-610 was used. This strain has a minimal inhibitory concentration value of 0.5 mg L(-1) against florfenicol. Fifteen groups of 40 fish each were challenged by bath with 1.7 x 10(5) CFU mL(-1) for 1 h. Three days following challenge, medication with florfenicol was introduced in 12 of the groups. The dosages used were 10 mg kg(-1) day(-1) for 10 consecutive days in marine or salmonid pellets, 10 mg kg(-1) day(-1) for five consecutive days in marine pellets or administered at days 1, 2, 4, 6 and 8 following initiation of treatment. Among challenged unmedicated fish mortality started at day 3 post-challenge reaching a final cumulative mortality of 77% at day 15. The experiment was terminated at day 26. In the medicated groups, the majority of deaths occurred from days 3-7 post-challenge reaching final cumulative mortalities of 31% and 52%, respectively, for the fish given marine and salmonid pellets for 10 consecutive days. The fish treated with medicated marine pellets for five consecutive days and at days 1, 2, 4, 6 and 8 (sequential feeding) following initiation of treatment had cumulative mortalities of 52% and 38%, respectively. Survival of medicated fish in all groups was significantly (P < 0.005) greater than survival of challenged unmedicated fish. Furthermore, a significant difference (P < 0.001) in survival was found between fish treated for 10 consecutive days using marine pellets and the groups using marine pellets for five consecutive days and salmonid pellets for 10 consecutive days. Twenty four hours following last medication, six fish had mean plasma concentrations of 3.3 +/- 1.7 and 3.5 +/- 2.8 microg mL(-1), respectively, in fish treated for 10 consecutive days using marine and salmonid pellets. Corresponding values for fish treated for five consecutive days and by sequential feeding were 2.2 +/- 2.3 and 1.7 +/- 0.7 microg mL(-1), respectively.

Smoking status moderates the contribution of social-cognitive and environmental determinants to adolescents' smoking intentions.

In this study, it was tested whether attitudes, self-efficacy, social influences and the perception of the school and home environments had different associations with intentions for adolescent non-smokers, occasional smokers and daily smokers. A regression model allowing for separate slopes of social-cognitive and environment variables accounted for 72% of the variation in intentions. For non-smokers, ease of refusing to smoke (beta = -0.06) and social influences favouring smoking (beta = 0.05) were linked to intentions. Occasional and daily smokers' intentions were associated with health consequences (beta = -0.05 and beta = -0.06, respectively) and ease of smoking/buying cigarettes (beta = 0.05 and beta = 0.24, respectively). Social influences favouring smoking (beta = 0.10) were also associated with intentions in daily smokers. In an extended model for current smokers (adjusted R(2) = 0.45), context-cued nicotine cravings (beta = 0.27) were linked to daily smokers', but not occasional smokers' intentions. The results suggest that motivating adolescents to abstain from or to quit smoking implies working on different combinations of determinants in non-smokers, occasional smokers and daily smokers. Interventions for daily smokers should supplement motivational techniques with stratagems that allow smokers to reduce the number of cravings they experience in specific contexts.

The role of physical workload and pain related fear in the development of low back pain in young workers: evidence from the BelCoBack Study; results after one year of follow up.

AIMS: To study the influence of work related physical and psychosocial factors and individual characteristics on the occurrence of low back pain among young and pain free workers. METHODS: The Belgian Cohort Back Study was designed as a prospective cohort study. The study population of this paper consisted of 716 young healthcare or distribution workers without low back pain lasting seven or more consecutive days during the year before inclusion. The median age was 26 years with an interquartile range between 24 and 29 years. At baseline, these workers filled in a questionnaire with physical exposures, work related psychosocial factors and individual characteristics. One year later, the occurrence of low back pain lasting seven or more consecutive days and some of its characteristics were registered by means of a questionnaire. To assess the respective role of predictors at baseline on the occurrence of low back pain in the following year, Cox regression with a constant risk period for all subjects was applied. RESULTS: After one year of follow up, 12.6% (95% CI 10.1 to 15.0) of the 716 workers had developed low back pain lasting seven or more consecutive days. An increased risk was observed for working with the trunk in a bent and twisted position for more than two hours a day (RR 2.2, 95% CI 1.2 to 4.1), inability to change posture regularly (RR 2.1, 95% CI 1.3 to 3.5), back complaints in the year before inclusion (RR 1.7, 95% CI 1.1 to 2.8), and high scores of pain related fear (RR 1.8, 95% CI 1.0 to 3.1). Work related psychosocial factors and physical factors during leisure time were not predictive. CONCLUSION: This study highlighted the importance of physical work factors and revealed the importance of high scores of pain related fear in the development of low back pain among young workers.

[Clinical application of portable spirometry in asthma].

OBJECTIVE: To investigate the clinical applications of portable spirometry in asthma. METHODS: Twenty patients with asthma were recruited from Peking Union Medical College Hospital. Flow-volume loop, simultaneous asthma symptoms, and mood were monitored three times a day for consecutive 14 days. RESULTS: In patients with a normal daytime spirometry, marked decline of forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) were observed at night and/or in the early morning. A within subject correlation analysis between FEV1, PEF, and asthma symptoms showed that the correlation between symptoms and airway obstruction was found only in seven out of twenty patients (35%). Four patients (20%) reported many symptoms with nearly normal portable spirometry. Accordingly, their symptoms were not correlated with FEV1 and PEF. This group of patients was defined as over-perceivers. On the contrary, another two patients (10%) did not report any symptoms while obvious airways obstruction was recorded by a portable spirometry. These patients were defined as under-perceivers. CONCLUSIONS: Dynamic monitoring of flow-volume loop with a portable spirometry is more accurate than routine lung function test in assessment of asthma severity. In addition, combined with simultaneous monitoring of symptoms, it would be of particularly helpful in identifying two specific types of asthma patients, e.g. over-perceivers and under-perceivers.

Complicaciones precoces de la cirugía del cáncer gástrico / Early complications of the surgery of gastric cancer

La cirugía del cáncer gástrico es un procedimiento complejo que no está libre de complicaciones graves y letales. El objetivo del presente estudio es describir la morbimortalidad asociada a gastrectomía por cáncer en los últimos años. Se revisan las historias de los pacientes operados de gastrectomía en un período de 5 años. Se encuentran 107 casos, de los cuales, se realiza cirugía con intención curativa en 90 (84,1 por ciento). La cifra global de morbilidad es 25,2 por ciento y la mortalidad 7,5 por ciento. La principal complicación post operatoria es la fístula esófago-yeyunal post gastrectomía total, con una incidencia de 17,6 por ciento y una letalidad de 44 por ciento. Otras complicaciones incluyen la peritonitis post operatoria, absceso intraabdominal, infección de herida operatoria y retardo del vaciamiento gástrico, entre otros. Destaca una baja incidencia de neumonía. Se encontró una tendencia favorable en gastrectomías con intención curativa vs. paliativa y en el uso de suturas mecánicas vs. manuales. La morbimortalidad se compara favorablemente a lo encontrado en la literatura y se mantiene una tendencia a la reducción al compararla con la experiencia ya publicada por el mismo grupo quirúrgico.

[Medically unexplained dyspnea in children: a review of 34 cases].

OBJECTIVE: Medically unexplained dyspnea is common in adult and accounts for 14% patients complaining of dyspnea. Its occurrence in children is seldom recognized. In the present paper, 34 children with medically unexplained dyspnea (age 10 to 18 years) seen in Peking Union Medical College Hospital from 1996 to 2002 are reported. METHODS: The diagnosis of medically unexplained dyspnea was clinical: it was based on the presence of dyspnea and other complaints which cannot be explained by an organic disease. The patients answered Nijmegen questionnaire and state and trait anxiety (STAI), and performed hyperventilation provocation test. Twenty sessions of breathing therapy were applied and 13 out of 34 children were followed up after the therapy. RESULTS: Among the children, 75% started to have symptoms at the age of 13 to 16 years, though the age of first episode could be as early as 8 years. In most of the cases, the course was chronic clinically. In addition to marked dyspnea, their clinical profile included symptoms of hyperventilation i.e. blurred vision, dizziness, tingling, stiff fingers or arm. The symptoms of anxiety were less frequent in children and accordingly the level of anxiety evaluated by means of STAI was lower in children compared to adult patients. The precipitating psychological factors appeared to be related to middle school competition. Pressure from exams, reprimand from stern and unsympathetic teachers coupled with high parental expectation could be emotionally damaging to psychologically susceptible children. Thirteen patients were followed up after 2-3 months of breathing therapy with emphasis on abdominal breathing and slowing down of expiration. After therapy, the sum score of the Nijmegen Questionnaire was markedly decreased. Dyspnea and symptoms of hyperventilation were improved. The level of anxiety was minimally modified. CONCLUSION: The cases illustrated the need for careful diagnostic evaluation and treatment because of the high rate of chronicity of the disorder.

Medically unexplained dyspnea: psychophysiological characteristics and role of breathing therapy.

BACKGROUND: Medically unexplained dyspnea occurs commonly in medical settings and remains poorly understood. This study was conducted to investigate the psychophysiological characteristics of medically unexplained dyspnea and the efficacy of breathing retraining for these patients. METHODS: A group of patients with medically unexplained dyspnea were compared to patients with a variety of organic lung diseases and healthy subjects. In another group of patients, the influence of breathing therapy on complaints, anxiety, and breath-holding was evaluated for an average of 1.5 years. RESULTS: Patients with medically unexplained dyspnea reported more intense dyspnea than patients with a variety of organic lung diseases. Additionally, they were anxious and presented a broad range of symptoms in daily life and under challenge, for instance voluntary hyperventilation. More than one third of them qualified for panic disorder. They had shorter breath-holding time at rest, less increase in breath-holding time and higher chances of showing a "paradoxical" decrease of breath-holding time after hyperventilation. A combination of PaO2, forced expiratory volume in one second (FEV1), and anxiety measures distinguished them from organic dyspnea. Breathing retraining profoundly improved their symptoms and decreased the level of state and trait anxiety. Moreover, they better tolerated the voluntary hyperventilation and the symptoms induced were also markedly decreased after therapy. Breath-holding time was prolonged and PetCO2 in a representative group of patients increased. CONCLUSIONS: Patients with medically unexplained dyspnea appear to have the feature of a "psychosomatic" patient: an anxious patient with a wide variety of symptoms of different organ systems that do not have an organic basis. They can be distinguished from organic dyspnea using a small set of physiological and psychological measures. Breathing retraining turns out to be an effective therapy for those "difficult to treat patients".