Effect of maximum exercise on left ventricular deformation and its correlation with cardiopulmonary exercise capacity in competitive athletes.

BACKGROUND: Global longitudinal strain (GLS) and global myocardial work index (GWI) allow early detection of subclinical changes in left ventricular (LV) systolic function. The aim of the study was to investigate the immediate effects of maximum physical exercise by different exercise testing methods on early post exercise LV deformation parameters in competitive athletes and to analyze their correlation with cardiopulmonary exercise capacity. METHODS: To reach maximum physical exercise, cardiopulmonary exercise testing (CPET) was performed by semi-recumbent ergometer in competitive handball players (n = 13) and by treadmill testing in competitive football players (n = 19). Maximum oxygen uptake (VO2max) indexed to body weight (relative VO2max) was measured in all athletes. Transthoracic echocardiography and blood pressure measurements were performed at rest and 5 min after CPET in all athletes. GLS, GWI and their changes before and after CPET (ΔGLS, ΔGWI) were correlated with (relative) VO2max. RESULTS: In handball and football players, GLS and GWI did not differ significantly before and after CPET. There were no significant correlations between GLS and relative VO2max, but moderate correlations were found between ΔGWI and relative VO2max in handball (r = 0.631; P = 0.021) and football players (r = 0.592; P = 0.008). Furthermore, handball (46.7 ml/min*kg ± 4.7 ml/min*kg vs. 37.4 ml/min*kg ± 4.2; P = 0.004) and football players (58.3 ml/min*kg ± 3.7 ml/min*kg vs. 49.7 ml/min*kg ± 6.8; P = 0.002) with an increased ΔGWI after CPET showed a significant higher relative VO2max. CONCLUSION: Maximum physical exercise has an immediate effect on LV deformation, irrespective of the used testing method. The correlation of relative VO2max with ΔGWI in the early post exercise period, identifies ΔGWI as an echocardiographic parameter for characterizing the current individual training status of athletes.

The impact of upright posture on left ventricular deformation in athletes.

Besides LV ejection fraction (LVEF), global longitudinal strain (GLS) and global myocardial work index (GWI) are increasingly important for the echocardiographic assessment of left ventricular (LV) function in athletes. Since exercise testing is frequently performed on a treadmill, we investigated the impact of upright posture on GLS and GWI. In 50 male athletes (mean age 25.7 ± 7.3 years) transthoracic echocardiography (TTE) and simultaneous blood pressure measurements were performed in upright and left lateral position. LVEF (59.7 ± 5.3% vs. 61.1 ± 5.5%; P = 0.197) was not affected by athletes' position, whereas GLS (- 11.9 ± 2.3% vs. - 18.1 ± 2.1%; P < 0.001) and GWI (1284 ± 283 mmHg% vs. 1882 ± 247 mmHg%; P < 0.001) were lower in upright posture. Longitudinal strain was most frequently reduced in upright posture in the mid-basal inferior, and/or posterolateral segments. Upright posture has a significant impact on LV deformation with lower GLS, GWI and regional LV strain in upright position. These findings need to be considered when performing echocardiography in athletes.

Responsiveness to oral prednisolone in severe asthma is related to the degree of eosinophilic airway inflammation.

BACKGROUND: Patients with severe asthma appear relatively corticosteroid resistant. Corticosteroid responsiveness is closely related to the degree of eosinophilic airway inflammation. The extent to which eosinophilic airway inflammation in severe asthma responds to treatment with systemic corticosteroids is not clear. OBJECTIVE: To relate the physiological and inflammatory response to systemic corticosteroids in asthma to disease severity and the baseline extent of eosinophilic inflammation. METHODS: Patients with mild/moderate and severe asthma were investigated before and after 2 weeks of oral prednisolone (Clintrials.gov NCT00331058 and NCT00327197). We pooled the results from two studies with common protocols. The US study contained two independent centres and the UK one independent centre. The effect of oral corticosteroids on FEV1 , Pc20, airway inflammation and serum cytokines was investigated. Baseline measurements were compared with healthy subjects. RESULTS: Thirty-two mild/moderate asthmatics, 50 severe asthmatics and 35 healthy subjects took part. At baseline, both groups of asthmatics had a lower FEV1 and Pc20 and increased eosinophilic inflammation compared to healthy subjects. The severe group had a lower FEV1 and more eosinophilic inflammation compared to mild/moderate asthmatics. Oral prednisolone caused a similar degree of suppression of eosinophilic inflammation in all compartments in both groups of asthmatics. There were small improvements in FEV1 and Pc20 for both mild/ moderate and severe asthmatics with a correlation between the baseline eosinophilic inflammation and the change in FEV1 . There was a ~50% reduction in the serum concentration of CXCL10 (IP-10), CCL22 (MDC), CCL17 (TARC), CCL-2 (MCP-1) and CCL-13 (MCP-4) in both asthma groups after oral corticosteroids. CONCLUSIONS AND CLINICAL RELEVANCE: Disease severity does not influence the response to systemic corticosteroids. The study does not therefore support the concept that severe asthma is associated with corticosteroid resistance. Only baseline eosinophilic inflammation was associated with the physiological response to corticosteroids, confirming the importance of measuring eosinophilic inflammation to guide corticosteroid use.

Spontaneous osteonecrosis of the knee (SONK).

PURPOSE: Spontaneous osteonecrosis of the knee (SONK/Morbus Ahlback) mainly affects the medial condyle of elderly women. It is assumed that localized vascular insufficiency leads to necrosis of the subchondral bone with subsequent disruption of the nutrition supply to the cartilage above. The aetiology remains unclear in detail. Operative treatment procedures compete against non-operative strategies, whereas the outcome is unpredictable in many cases. METHOD: A consecutive case series of five patients suffering from SONK was analysed. All patients underwent a clinical examination, magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry scan, as well as laboratory analyses and visual analogue scale (VAS) evaluation. Our treatment regime is based on high-dose vitamin D administered orally and intravenous application of 3 mg ibandronate two times within 8 weeks. Another 8 weeks later, all patients were followed up including a follow-up MRI. RESULTS: Within 4 weeks, all patients were free of symptoms. The MRI follow-up showed remission of the bone marrow oedema in every case studied. VAS decreased significantly from 7.4 ± 1.0 pre-interventional to 0.8 ± 1.0 post-interventional. No allergic reactions or other side effects were documented. CONCLUSION: We showed that our treatment regime not only eliminated the pathological findings in the MRI of all cases studied, but also decreased the pain level and functional limitations within a short-time period. LEVEL OF EVIDENCE: IV.

Influence of non-traumatic thoracic and lumbar vertebral fractures on sagittal spine alignment assessed by radiation-free spinometry.

UNLABELLED: Due to missing indications for specific diagnostics, the majority of non-symptomatic vertebral fractures are not diagnosed. This study shows the ability of radiation-free spinometry to assess sagittal spine parameters to raise suspicion for new non-traumatic thoracic and lumbar vertebral fractures and indicate specific diagnostics. INTRODUCTION: The primary aim of this study was to investigate the accuracy of radiation-free spinometry to predict new non-traumatic vertebral fractures (VF) by the assessment of thoracic kyphosis (TK), lumbar lordosis (LL), and trunk inclination. METHODS: Three hundred sixty-one patients (278 females and 83 males; age, 67.0 ± 8.6 years) were enrolled. In 86 women and 24 men, at least one non-traumatic VF was confirmed by radiography, MRI, and/or CT. Spinometry (video rasterstereography) was used to assess TK, LL, and trunk inclination. Receiver operating characteristic (ROC) and multivariate logistic regression analyses were performed to test the influence of age, sex, number, location, and grade of fractures on sagittal spine alignment. RESULTS: TK, LL, and trunk inclination were associated with advancing age (p < 0.05). Patients with prevalent thoracic and lumbar VFs showed increased TK (p < 0.001), decreased LL (p < 0.001), and increased trunk inclination (p < 0.001) in comparison to patients without VFs. ROC analysis revealed that the combination of TK and LL presented with the best predictive accuracy to raise suspicion for new grade 2 or grade 3 VFs in the thoracic and the lumbar spine (AUC, 0.752-0.771). Odds ratio (OR) showed an increased risk for VFs with increased TK (OR, 1.05-1.11; p < 0.001) and LL (1.05-1.07; p < 0.001) in specified regions of interest. A TK <50° (sensitivity, 88-100 %; specificity, 23-25 %) and LL (78-92 %; 24-27 %) were considered as appropriate cutoffs for future screening. CONCLUSION: Spinometry showed better predictive accuracy than historical height loss. Severe changes of TK and LL may help to raise suspicion of new VFs radiation-free and indicate proper diagnostics, such as radiographs, MRI, or CT.

Delayed ultraviolet erythema not suppressed by oral prednisolone: a randomized crossover study.

BACKGROUND: The anti-inflammatory potency of topical dermatological corticosteroids in suppressing ultraviolet (UV) erythema is routinely measured. No such model exists to assess the potency of systemically administered steroids. OBJECTIVE: To determine whether or not suppression of delayed UV erythema by a systemic corticosteroid could provide a useful model for assessing the anti-inflammatory potency of systemic corticosteroids. METHODS: We conducted a randomized, placebo-controlled, patient and assessor blinded, crossover study of oral prednisolone effects on the delayed UV-induced erythemal response in normal subjects. Six healthy volunteers were phototested with a xenon arc monochromator and then dosed with 30 mg of oral prednisolone or matching placebo daily for 4 days. Repeat phototesting was performed on the 4th day of dosing. The minimal erythema dose (MED) was assessed immediately after test UV doses were administered and 24 h later. After a 2-week washout period, the dosing and testing were repeated in a crossover fashion. RESULTS: A suppression index (SI) [1/(baseline MED value divided by on prednisolone/placebo value)] allowed comparison of the degree of suppression on and off prednisolone. Oral prednisolone did not significantly suppress the threshold UV erythema response (MED). We may have missed small effects in this study and possibly a larger dose or a longer duration of corticosteroid would have had an effect. Possibly, assessment of corticosteroid potency in suppressing established UV erythema rather than on the development of threshold erythema would have yielded different results. CONCLUSION: The threshold UV erythema suppression model assessed in this study could not distinguish between oral prednisolone and placebo. This UV-erythema suppression test system is not promising as a model to test the anti-inflammatory potency of systemic steroids.

The rapamycin analogue SDZ RAD attenuates bleomycin-induced pulmonary fibrosis in rats.

Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix proteins within the pulmonary interstitium. The new macrolide immunosuppressant SDZ RAD, a rapamycin analogue, inhibits growth-factor dependent proliferation of mesenchymal cells and might therefore be of therapeutic interest for the treatment of fibrotic lung disease. In this study the effect of SDZ RAD on lung-collagen accumulation in the bleomycin model of pulmonary fibrosis in rats was investigated. SDZ RAD (2.5 mg x kg(-1) x day(-1)) or drug vehicle were administered orally by daily gavage. Successful dosing was confirmed by measuring splenic weight. Total lung-collagen content was measured by high-performance liquid chromatographic quantitation of hydroxyproline. In animals given bleomycin and drug vehicle, total lung collagen was increased by 182+/-11% (mean+/-SEM) compared with saline controls at 14 days (p<0.001). The increase in lung-collagen accumulation was reduced by 75+/-12% (p<0.01) in animals given SDZ RAD and was accompanied by a concomitant 56+/-6% (p<0.001) reduction in lung weight. SDZ RAD is currently in clinical trials for the prevention of solid organ graft rejection, another condition characterized by excessive extracellular matrix production. The authors propose that SDZ RAD warrants evaluation as a novel therapeutic agent for fibrotic lung disease.

Direct thrombin inhibition reduces lung collagen, accumulation, and connective tissue growth factor mRNA levels in bleomycin-induced pulmonary fibrosis.

Dramatic activation of the coagulation cascade has been extensively documented for pulmonary fibrosis associated with acute and chronic lung injury. In addition to its role in hemostasis, thrombin exerts profibrotic effects via activation of the major thrombin receptor, protease-activated receptor-1. In this study, we examined the effect of the direct thrombin inhibitor, UK-156406 on fibroblast responses in vitro and on bleomycin-induced pulmonary fibrosis in rats. UK-156406 significantly inhibited thrombin-induced fibroblast proliferation, procollagen production, and connective tissue growth factor (CTGF) mRNA levels when used at equimolar concentration to the protease. Thrombin levels in bronchoalveolar lavage fluid and expression of thrombin and protease-activated receptor-1 in lung tissue were increased after intratracheal instillation of bleomycin. The characteristic doubling in lung collagen in bleomycin-treated animals (38.4 +/- 2.0 mg versus 17.1 +/- 1.4 mg, P < 0.01) was preceded by significant elevations in alpha1(I) procollagen and CTGF mRNA levels (3.0 +/- 0.4-fold and 6.3 +/- 0.4-fold respectively, (P < 0.01), and total inflammatory cell number. UK-156406, administered at an anticoagulant dose, attenuated lung collagen accumulation in response to bleomycin by 35 +/- 12% (P < 0.05), inhibited alpha1(I) procollagen and CTGF mRNA levels by 50% and 35%, respectively (P < 0.05), but had no effect on inflammatory cell recruitment. This is the first report showing that direct thrombin inhibition abrogates lung collagen accumulation in bleomycin-induced pulmonary fibrosis.

Medical-care costs associated with posttraumatic stress disorder in Vietnam veterans.

OBJECTIVE: This study examined the relationship between medical-care costs of Vietnam veterans and predictor factors, including posttraumatic stress disorder (PTSD). METHOD: We merged medical-care cost data from the Department of Veterans' Affairs and the Health Insurance Commission with data from an epidemiological study of 641 Australian Vietnam veterans. Posttraumatic stress disorder and other factors were examined as predictors of medical-care cost using regression analysis. RESULTS: We found that a diagnosis of PTSD was associated with medical costs 60% higher than average. Those costs appeared to be partly associated with higher treatment costs for physical conditions in those with PTSD and also related mental health comorbidities. Major predictors of medical-care cost were age ($137 per year for each 5-year increase in age) and number of diagnoses reported ($81 to $112 per year for each diagnosis). Mental health factors such as depression ($14 per year for each symptom reported) and anxiety ($27 per year for each symptom reported) were also important predictors. CONCLUSIONS: The findings indicate that, however they are incurred, high healthcare and, presumably, also economic and personal costs are associated with PTSD. There is an important social obligation as well as substantial economic reasons to deal with these problems. From both perspectives, continued efforts to identify and implement effective prevention and treatment programs are warranted.

Fibroproliferation occurs early in the acute respiratory distress syndrome and impacts on outcome.

The fibroproliferative phase of acute respiratory distress syndrome (ARDS) has traditionally been regarded as a late event but recent studies that suggest increased lung collagen turnover within 24 h of diagnosis challenge this view. We hypothesized that fibroproliferation is initiated early in ARDS, characterized by the presence of fibroblast growth factor activity in the lung and would relate to clinical outcome. Patients fulfilling American/European Consensus Committee criteria for ARDS and control patients ventilated for non-ARDS respiratory failure underwent bronchoalveolar lavage (BAL) and serum sampling within 24 h of diagnosis and again at 7 d. The ability of BAL fluid (BALF) to stimulate human lung fibroblast proliferation in vitro was examined in relation to concentrations of N-terminal peptide for type III procollagen (N-PCP-III) in BALF/serum and clinical indices. At 24 h, ARDS lavage fluid demonstrated potent mitogenic activity with a median value equivalent to 70% (range 31-164) of the response to serum, and was significantly higher than control lavage (32% of serum response, range 11-42; p < 0.05). At 24 h, serum N-PCP-III concentrations were elevated in the ARDS group compared with control patients (2.8 U/ml; range 0.6-14.8 versus 1.1 U/ml; range 0.4-3.7, p < 0.0001) as were BALF N-PCP-III concentrations (2.9 U/ml; range 0. 6-11.4 versus 0.46 U/ ml; range 0.00-1.63, p < 0.01). In addition, BALF N-PCP-III concentrations at 24 h were significantly elevated in nonsurvivors of ARDS compared with survivors (p < 0.05). At 7 d, the mitogenic activity remained elevated in the ARDS group compared with control (p < 0.05) and was also significantly higher in ARDS nonsurvivors compared with survivors (67%; range 45-120 versus 31%; range 16-64, p < 0.05). These data are consistent with the hypothesis that fibroproliferation is an early response to lung injury and an important therapeutic target.

Distress experienced by participants during an epidemiological survey of posttraumatic stress disorder.

We examined the potential for epidemiological studies of mental disorders, specifically of posttraumatic stress disorder (PTSD), to cause further harm to participants involved. Of 1,000 randomly selected Australian Vietnam veterans, 641 agreed to participate in an epidemiological survey. Participants were asked about distress experienced during the interview when traumatic events were raised. Significant distress attributed to the interview was reported by 75.3% of those with current PTSD, 56.5% of those with past PTSD, and 20.6% of those with no PTSD diagnosis. Distress did not affect participants' use of medical services following the interview nor did it affect their willingness to continue participating in the study. We concluded that research interviews about PTSD may cause short-term distress, but found no evidence of long-term harm.

Angiotensin II is mitogenic for human lung fibroblasts via activation of the type 1 receptor.

The expression of renin-angiotensin system components and the elevation of angiotensin-converting enzyme (ACE) in a number of fibrotic lung diseases suggests angiotensin II (AII) could play a role in the pathogenesis of pulmonary fibrosis. However, the effect of AII on lung fibroblasts has not previously been assessed and the mechanisms by which AII induces cell proliferation in mesenchymal cells are not fully understood. We have examined the ability of AII to stimulate fetal and adult human lung fibroblast proliferation in vitro. In particular, we have assessed the receptor subtypes involved and the possible autocrine role of transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF), two recognized fibroblast mitogens. Angiotensin type 1 (AT1), but not type 2, receptors were identified on fetal and adult human lung fibroblasts by immunocytochemistry. AII (1 microM) increased DNA synthesis (determined by [(3)H]thymidine incorporation) in fetal and adult cells by 211 +/- 18% and 150 +/- 14%, respectively (p < 0.01), and was inhibited by a specific AT1 receptor antagonist, Losartan (74 +/- 14%). A proliferative response to AII was confirmed by direct cell counts. Subsequently, fibroblasts were incubated with neutralizing antibodies to TGF-beta and PDGF. Anti-TGF-beta antibodies inhibited AII-induced DNA synthesis by 73 +/- 13%. However, no effect was seen with anti-PDGF antibodies. In conclusion, we have shown that angiotensin II induces human lung fibroblast proliferation in vitro via activation of the AT1 receptor and involves the autocrine action of TGF-beta.

Adult familial cryptogenic fibrosing alveolitis in the United Kingdom.

BACKGROUND: Familial cases of cryptogenic fibrosing alveolitis (CFA) have previously been reported; however, the prevalence and genetic background of this disorder are not known. The clinical and epidemiological findings of 25 families identified within the UK are reported. METHODS: Adult pulmonary physicians in the UK were asked to identify all families under their care in which two or more individuals had been diagnosed with fibrosing alveolitis of unknown cause. A detailed structured questionnaire was sent to each proband to delineate possible environmental/occupational exposures and to obtain complete pedigree data. Physicians were also asked to provide clinical and diagnostic information. RESULTS: Twenty five families were identified comprising 67 cases. Suitable data for analysis were available for 21 families (57 cases). The male:female ratio was 1. 75:1 (p<0.05). A high resolution computed tomographic (HRCT) scan was performed in 93% and a diagnosis of CFA confirmed on biopsy specimens in 32%. The mean age at diagnosis was 55.5 (2.5) years. Fifty percent of cases were ever smokers and 18% had been diagnosed as asthmatic. Exposure to known fibrogenic agents was recorded by 36% of patients. Clinical signs/symptoms and histological findings were indistinguishable from non-familial cases. CONCLUSIONS: This study represents the largest cohort of familial CFA cases reported to date and confirms a prevalence of 1.34 cases per 10(6) in the UK population. Although rare, such cases represent an important subgroup in which a genetic susceptibility to pulmonary fibrosis is particularly evident. Familial patients are younger at diagnosis but otherwise indistinguishable from non-familial cases. The mode of inheritance is as yet unclear but a number of genetic loci are likely to be involved and are the subject of ongoing studies.

Combat, dissociation, and posttraumatic stress disorder in Australian Vietnam veterans.

The specificity of various wartime stressors for different posttraumatic stress disorder (PTSD) symptoms is inconsistently reported in the literature. Combat, wounding, and peritraumatic dissociation have not been assessed together in their effects on each of the various PTSD symptom clusters. This cohort study of a random sample of male Australian Army Vietnam veterans yielded psychiatric assessments of 641 subjects. PTSD measures comprised symptom criteria for reexperiencing, numbing and avoidance, hyperarousal, and PTSD diagnosis both lifetime and current within the past month. Logistic regression is used to examine the effects of combat, wounding, and peritraumatic dissociation together on PTSD. Combat experiences comprised four components derived from a principal components analysis of combat experiences: direct combat exposure, exposure to death and injury, exposure to civilian death and injury, and exposure to mutilation. Each was differentially related to reexperiencing, avoidance, hyperarousal, and PTSD diagnosis. Being wounded was not related to lifetime or current PTSD and peritraumatic dissociation was related to all diagnostic components of PTSD in the presence of other variables.

Posttraumatic stress disorder and other predictors of health care consumption by Vietnam veterans.

A total of 641 randomly selected Australian veterans of the Vietnam War were interviewed about their use of health care in the previous two weeks to determine what factors contributed to health care consumption. Seventy-three variables were examined by univariate linear regression and then grouped into seven categories relating to age, physical and mental health, predisposition to posttraumatic stress disorder (PTSD), deployment and repatriation experiences, and membership in veterans groups. PTSD was associated with an additional cost of $79 in health care for the two-week period. Each physical diagnosis was associated with an additional $28. Alcohol consumption was not related to health care costs. Other important variables contributing to costs were depression, educational status, the quality of the repatriation experience, and social support.

DRG cost weights--getting it right.

Inadequate cost weights are a major problem in casemix funding systems. Clinicians should understand the basis for the cost weights underpinning the hospital payment system in their State and their own hospital. Clinician managers need valid patient costing data if they are to benchmark and improve cost-effectiveness while maintaining and enhancing quality. The cost model approach for determining cost weights has inherent limitations, and, the alternative, detailed patient costing, requires efficient hospital information technology systems. A simplified approach to patient costs, which uses existing hospital data systems, may be useful for smaller hospitals. A better classification system and funding formulas incorporating reliable cost weights derived from patient costing should overcome many of the deficiencies in the current casemix payments systems.

Postwar experiences and treatment-seeking behavior in a community counselling setting.

Previous research investigating the impact of postwar experiences on Vietnam veterans has focused on veteran morbidity. This emphasis has meant that the impact of these factors on treatment-seeking behavior has received little empirical attention. This study examined the association between postwar factors and treatment-seeking behavior in a sample of 692 Australian Vietnam veterans. Logistic regression analyses were used to compute the odds ratios associated with postwar experiences and self-referral to a community-based counselling service. Results suggest that veterans who reported experiencing negative feelings toward others when they first arrived home were more likely to seek treatment. Other factors, such as a veteran's perception of societal attitudes and the reception they received, were not associated with treatment-seeking behavior.

Risk factors for posttraumatic stress disorder in Australian Vietnam veterans.

OBJECTIVE: The aims of this paper are to determine the risk factors for combat-related posttraumatic stress disorder (PTSD) and to examine the relative contribution of pre-military factors, pre-trauma psychiatric diagnoses, military factors such as combat posting, and combat and casualty stress exposure. METHOD: An epidemiological cohort study using standardised psychiatric, social and health interviews was undertaken with a national random sample of male Australian Army Vietnam veterans. Multivariate logistic regression was used to examine the relative contribution of factors derived from interview and from military records in four categories: pre-enlistment circumstances including home life, education, major life stress; pre-Vietnam psychiatric diagnoses; military experiences before and during Vietnam; and combat and stress experiences. RESULTS: Of the 128 data items examined, significant associations were found for 39, in addition to combat stress. Pre-enlistment items accounted for about 3% of the deviance towards PTSD diagnosis, pre-enlistment psychiatric diagnosis about 13%, military variables about 7% and combat stress about 18%; all factors together accounted for 42%. CONCLUSIONS: The results confirm that pre-military and military variables make only a small but significant contribution to PTSD either alone or after controlling for combat stress; that psychiatric diagnoses of depression, dysthymia and agoraphobia make strong contributions to PTSD; but that combat stress makes the largest contribution even after controlling for the effects of other variables. Psychiatric diagnoses and combat stress appear to be independent in their effects on PTSD.

Posttraumatic stress disorder and comorbidity in Australian Vietnam veterans: risk factors, chronicity and combat.

OBJECTIVE: The objective of this study was to examine the relationship between combat-related posttraumatic stress disorder (PTSD) and comorbid DSM-III-R psychiatric diagnoses to determine commonalities in risk factors, relative onsets and the role of combat exposure. METHOD: An epidemiological cohort study using standardised psychiatric, social and health interviews was undertaken with a national random sample of male Australian Army Vietnam veterans. Interviews and searches of military records yielded risk factors for PTSD, which were examined for association with each psychiatric diagnosis. Relative onsets of PTSD and each Diagnostic Interview Schedule diagnosis were compared. Comorbidity odds ratios were adjusted for combat exposure effects using logistic regression, and the relation between each diagnosis and combat was assessed after controlling for PTSD. RESULTS: Commonality of risk factor profile was evident for several diagnoses, and for many their onset preceded PTSD onset. Combat was independently related to only a few diagnoses after controlling for PTSD, and PTSD remained strongly associated with several conditions after controlling for combat exposure. CONCLUSIONS: The analysis suggests that the disorders that may constitute risk factors or vulnerabilities for PTSD comprise depression and dysthymia, antisocial personality disorder, agoraphobia and simple phobia, while those that may be consequent on PTSD are panic and generalised anxiety disorder, drug use disorders and somatoform pain disorder. Alcohol and drug use disorders and social phobia may have a mixed aetiology, while obsessive-compulsive disorder may be serendipitously related to PTSD through an association with risk of combat. Gambling disorder is unrelated.