Sudden death after emotional stress: a case history and literature review.

An 84-year old women in no apparent distress suddenly died, unexpectedly, an hour after being notified of having a malignancy. Behavioural scientists have long speculated about the relationship between emotional stress and sudden death. We reviewed the presently available evidence regarding the neurophysiologic mechanisms of sudden death after emotional stress.

Plasma arginine vasopressin and atrial natriuretic peptide concentration in patients with hyponatremia at diagnosis and following treatment.

BACKGROUND: Much evidence for arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) in the pathogenesis of hyponatremia in humans is based on single measurements. To study the roles of AVP and ANP in the pathogenesis and recovery of hyponatremia, sequential measurements of ANP and AVP were taken during treatment in a group of hyponatremic patients with different etiologies. METHODS: Consecutive adult patients with hyponatremia (serum Na <130 mmol/l) and healthy controls were studied. Volume status was determined by clinical and laboratory criteria. Plasma AVP and ANP, fractional sodium excretion, and urine osmolality were determined daily until serum Na was above 135 mmol/l or for at most 7 days. RESULTS: A total of 16 controls and 40 hyponatremic patients (12 normovolemic, 9 hypervolemic, and 19 hypovolemic) were studied. Patients' plasma AVP on the first day [1.0 (0.3-2.3) ng/l] and on the last day [1.1 (0.3-2.5) ng/l] of the study did not differ from that of controls [0.7 (0.5-1.0) ng/l]. Serum sodium concentration increased significantly in patients between the first and the last day. Patients had significantly lower ANP concentrations, both on the first day [25 (15-46) ng/l] and on the last day [29 (17-46) ng/l], than controls [41 (28-51) ng/l]. Plasma AVP was elevated relative to serum osmolality on the first day and to a lesser extent on the last day of the study. CONCLUSIONS: AVP is inappropriately high in a majority of hyponatremic patients. Plasma AVP and ANP concentrations do not change during treatment in hyponatremic patients despite a significant increase in serum osmolality. A low ANP concentration in clinically normovolemic and hypovolemic patients indicates volume depletion, which may lead to baroreceptor-stimulated AVP secretion.

Treating proteinuria in a diabetic patient despite hyperkalaemia due to hyporeninaemic hypoaldosteronism.

Diabetes mellitus is a common cause of hyporeninaemic hypoaldosteronism that might result in significant hyperkalaemia. We describe a patient with diabetic nephropathy and proteinuria who developed a remarkable hyperkalaemia on treatment with an angiotensin-receptor blocker. The management of hyperkalaemia and the pathophysiological background of hyporeninaemic hypoaldosteronism are discussed.

[Three patients with autoimmune hepatitis: the importance of early diagnosis and remission]. / Drie vrouwen met auto-immune hepatitis: het klinisch belang van tijdige diagnose en van remissie.

A 70-year-old woman presented with impaired memory and depressive symptoms and two women aged 53 and 30 years, respectively, presented with general malaise and fatigue. All were diagnosed with and treated for autoimmune hepatitis (AIH). The first patient developed a relapse during treatment withdrawal; she recovered and maintained remission after the initial dose of medication had been restarted and the medication was tapered more gradually. The second patient had an incomplete remission and later developed liver failure; she was eligible for a liver transplant. The third woman became pregnant during treatment and developed a relapse after delivery; remission was induced and maintained after the immunosuppression was temporally increased. AIH is a chronic progressive liver disease characterised by abnormal serum levels of liver enzymes, hypergammaglobulinaemia, auto-antibodies against cell nuclei (ANA), smooth muscle (SMA), or liver and kidney microsomes (LKM), interface hepatitis and the absence of other chronic liver disease. Early diagnosis is essential because therapy can markedly improve prognosis. However, there is no specific diagnostic test for AIH. It is important to induce and maintain remission with immunosuppressive therapy.

A mediastinal mass: Graves' disease related thymic hyperplasia.

A 35-year-old woman presented with symptoms of pulmonary embolism and thyrotoxicosis. Computed tomography of the chest ruled out pulmonary embolism but showed an incidental mediastinal mass. Graves' disease was confirmed and the mediastinal mass was ascribed to associating thymic hyperplasia. Treatment of Graves' thyrotoxicosis resulted in a spontaneous shrinkage of the mediastinal mass. Although it is relatively unknown, thymic hyperplasia is a normal and reversible manifestation of Graves' disease.

[Report from the Health Council of the Netherlands on the chronic fatigue syndrome: moving away from the body-mind dichotomy with a view to effective prevention and treatment]. / Gezondheidsraadrapport 'Het chronische-vermoeidheidssyndroom'; terechte afstand van de lichaam-geestdichotomie met het oog op effectieve preventie en behandeling.

The Health Council of the Netherlands has issued a report on the chronic fatigue syndrome (CFS). CFS is a real and seriously debilitating condition which imposes limitations on an individual's personal, occupational and social functioning. It is a syndrome of unknown aetiology without physical signs or biological markers. Although there is no disease, patients both feel ill and give the appearance of being ill. There is no consensus on whether CSF patients are able to work or whether they should be entitled to social security benefits. An imbalance between demand and coping is central in CFS, with stress as an important intermediary factor. It is little use concluding that unexplained signs are 'psychological' or that 'I cannot find anything wrong with you so you must be healthy'. The classical view that mind and body are separate systems is outmoded. The bio-psycho-social model of disease may be helpful in describing the interaction between body, mind and circumstance. Putting the CFS patient at ease and explaining the pathophysiology of the symptoms is a useful approach but many patients and patient associations are still very somatically orientated, thereby sustaining the condition. However, in patients who accept that their problems may be stress-induced and are prepared to participate in therapy, some therapies have been proven to be effective, notably cognitive behavioural therapy.

[Integration of training in pharmacology and pharmacotherapy in the medical curriculum in Leiden, the Netherlands]. / Integratie van onderwijs in farmacologie en farmacotherapie in het geneeskundecurriculum in Leiden.

In the new medical curriculum at Leiden University Medical Centre, the Netherlands, two aspects of the training in pharmacology and pharmacotherapy--the acquisition of knowledge and its application--have been integrated. On the basis of the approved subject matter and goals, four computer programmes were developed: the Teaching Resource Centre (TRC) Pharmacology database, the interactive TRC teaching programme, the Individual Therapy: Evaluation and Plan (ITEP), and the relational curriculum database. Together, these programmes provide the necessary knowledge in pharmacodynamics and pharmacokinetics, pharmacotherapy and the mechanisms of drug action, as well as possibilities for monitoring the educational process. The figures are created with the aid of a symbolic language, assuring a uniform presentation of all the information throughout the curriculum. Attention is also paid to the integration of these aspects with other subjects in the medical curriculum. Implementation of the teaching system in pharmacology was started at the beginning of 2001. Currently, the TRC database contains almost all the subject matter that is planned to be included. The next step in the process will be the assessment of both the knowledge and its application. TRC Pharmacology is a new method of integrating basic knowledge of pharmacology and pharmacotherapy in a medical school curriculum.

Hyponatremia in intracranial disorders.

Hyponatremia is a common electrolyte disturbance following intracranial disorders. Hyponatremia is of clinical significance as a rapidly decreasing serum sodium concentration as well as rapid correction of chronic hyponatremia may lead to neurological symptoms. Especially two syndromes leading to hyponatremia in intracranial disorders need to be distinguished, as they resemble each other in many, but not all ways. These are the syndrome of inappropriate ADH secretion (SIADH) and the cerebral salt wasting syndrome (CSW). The syndrome of inappropriate ADH secretion is characterized by water retention, caused by inappropriate release of ADH, leading to dilutional hyponatremia. The cerebral salt wasting syndrome on the other hand, represents primary natriuresis, leading to hypovolemia and sodium deficit. SIADH should be treated by fluid restriction, whereas the treatment of CSW consists of sodium and water administration. However, in the literature there is abundant evidence that hyponatremia in intracranial diseases is mostly caused by CSW. Therefore, treatment with fluid and salt supplementation seems indicated in patients with intracranial disorders who develop hyponatremia and natriuresis.

The Reassurance Questionnaire (RQ): psychometric properties of a self-report questionnaire to assess reassurability.

BACKGROUND: The aim of this study was to develop a questionnaire that assessed the extent to which patients usually feel reassured by their attending physician. METHODS: The study population consisted of 204 subjects from the general population, 113 general practice patients, 130 general medical out-patients and 183 general medical patients with unexplained physical symptoms participating in an intervention study on the effect of cognitive behavioural therapy. RESULTS: Factor analysis yielded a one-factor solution. The internal consistency was moderate to high and the test-retest reliability was high. The convergent validity of the Reassurance Questionnaire (RQ) was satisfactory to good, but the scores on the RQ did not appear to differentiate between the general population, general practice patients and general medical out-patients. In medical out-patients with unexplained physical symptoms, the RQ discriminated well between hypochondriacal and non-hypochondriacal patients. Scores on the RQ tended to be associated with a bad outcome in terms of recovery of presenting symptoms at 1 year follow-up. There was no association between scores on the RQ and frequency of physician contact. In patients with unexplained physical symptoms treated with cognitive behavioural therapy, scores on the RQ decreased over a period of 6 months and 1 year. CONCLUSIONS: The RQ was demonstrated to have psychometrically sound properties and appeared to be a useful instrument to assess reassurability in medical patients.

Is alexithymia a risk factor for unexplained physical symptoms in general medical outpatients?

OBJECTIVE: Alexithymia is presumed to play an important predisposing role in the pathogenesis of medically unexplained physical symptoms. However, no research on alexithymia has been done among general medical outpatients who present with medically unexplained physical symptoms as their main problem and in which anxiety and depression have been considered as possible confounding factors. This study investigated whether patients with medically unexplained physical symptoms are more alexithymic than those with explained symptoms and whether, in patients with unexplained symptoms, alexithymia is associated with subjective health experience and use of medical services. METHODS: We conducted a cross-sectional study among patients attending an internal medicine outpatient clinic. All patients were given a standardized interview and completed a number of questionnaires. RESULTS: After complete physical examinations, 169 of 321 patients had unexplained physical symptoms according to two independent raters. Patients with medically unexplained symptoms more often had a mental disorder, but overall they were not more alexithymic. In patients with unexplained physical symptoms, alexithymia was not associated with subjective health experience or use of medical services. However, patients with both unexplained symptoms and a mental disorder who also denied any possible connection between emotional problems and their physical symptoms did have more alexithymic traits. CONCLUSIONS: In the majority of patients with medically unexplained physical symptoms, alexithymia does not play a role of clinical significance. Patients with unexplained physical symptoms are heterogeneous with respect to psychiatric syndrome pathology and probably also with respect to personality pathology.

The diagnostic and prognostic significance of the Whitely Index, the Illness Attitude Scales and the Somatosensory Amplification Scale.

The aim of this study was to assess the ability of the Whitely Index, Illness Attitude Scales and Somatosensory Amplification Scale to differentiate in patients with medically unexplained physical symptoms between hypochondriacal and non-hypochondriacal patients and to examine whether the scores on these questionnaires are predictive of long-term outcome in terms of recovery of presenting symptoms and number of visits to the general practitioner. The study population consisted of 183 consecutive patients, who presented with medically unexplained physical symptoms to a general medical out-patient clinic. The Health Anxiety subscale of the Illness Attitude Scales and the Whitely Index were best in discriminating between hypochondriacal and non-hypochondriacal patients. The sensitivity and specificity of the Health Anxiety subscale of the Illness Attitude Scales were 79% and 84%, and of the Whitely Index 87% and 72%. The Whitely Index was negatively associated with recovery rate at 1 year follow-up. The Illness Behaviour subscale of the Illness Attitude Scales appeared to be predictive of the number of visits to the general practitioner. These findings might have clinical implications in helping to distinguish in patients with medically unexplained symptoms those for whom there is a high chance of persistence of the symptoms and/or of high medical care utilization.

Unexplained physical symptoms: outcome, utilization of medical care and associated factors.

The aim of the study was to investigate the recovery and frequency of physician contact in patients with unexplained physical symptoms and to identify factors associated with persistent disorder. Of 100 consecutive patients who presented with medically unexplained symptoms to a general medical out-patient clinic, 81 participated in a follow-up study. The mean follow-up time was 15.2 months (S.D. 4.0). At follow-up, many of the patients with unexplained physical symptoms reported that they had recovered (30%) or improved (46%) with regard to their presenting symptoms. Female sex and a high number of symptoms predicted a bad outcome in terms of recovery. Persistence of symptoms was not related to the duration of the symptoms, type of presenting complaint or the presence of psychiatric disorder. Forty per cent of patients with unexplained symptoms did not visit their general practitioner on their own initiative in the year following the initial visit to the clinic. Medical care utilization appeared to be associated with female sex, age, number and duration of symptoms, fatigue and psychiatric disorder, especially somatoform disorders. However, the association of a high frequency of physician contact with female sex and psychiatric disorder was not sustained after controlling for possible confounding factors.

[Criteria for somatization studied in an outpatient clinic for general internal medicine]. / Criteria voor somatiseren onderzocht op een polikliniek voor algemene interne geneeskunde.

OBJECTIVE: To compare the evolution of bodily symptoms and the frequency of medical consultation using three different operational definitions of 'somatization'. DESIGN: Descriptive follow-up study. SETTING: General Internal Medicine Outpatient Clinic of Leiden University Hospital, the Netherlands. METHOD: Information about physical and psychic symptoms and about the somatic-medical diagnosis was collected in a group of 158 newly referred patients. The concept of 'somatization' was operationalized in three ways: a) seeking medical consultation for somatically unexplained symptoms; b) seeking medical consultation for somatically unexplained symptoms combined with an anxiety disorder or a depressive disorder according to the 'present state examination'; c) seeking medical consultation for somatically unexplained symptoms combined with a somatization disorder or hypochondria according to the Diagnostic and statistical manual of mental disorders (DSM) III R criteria. After a follow-up period of 1.2 years, information was collected from the entire study group about the evolution of the physical symptoms and the frequency of medical consultation. RESULTS: Patients with somatically unexplained symptoms combined with a somatization disorder or hypochondria were characterized in the follow-up by numerous physical symptoms and a high frequency of medical consultation. Compared with the other patients with unexplained symptoms, they visited the general practitioner during the follow-up period 2.5 times as often, saw specialists twice as often and were admitted to a 'somatic' hospital, 6 times as often. CONCLUSION: Using criteria of low restrictiveness for somatization, a large group of patients were identified with a relatively normal (average) illness behaviour. Using more restrictive criteria led to identification of a smaller group with more extreme illness behaviour.

A validation study of the Whitely Index, the Illness Attitude Scales, and the Somatosensory Amplification Scale in general medical and general practice patients.

The aim of this study was to assess the reliability and validity of the Whitely Index (WI), the Illness Attitude Scales (IAS), and the Somatosensory Amplification Scale (SAS). The study population consisted of 130 general medical outpatients, 113 general practice patients, and 204 subjects from the general population. The factorial structure of the IAS appeared to consist of two subscales, namely Health Anxiety and Illness Behaviour. The internal consistency and stability of the three questionnaires were satisfactory, and their scores were highly intercorrelated. Scores on the WI and Health Anxiety subscale of the IAS declined significantly from general medical outpatients, through general practice patients to subjects from the general population. This might imply that medical care utilisation is related to hypochondriasis. A prospective study is needed to determine whether health anxiety contributes to the decision to seek medical care or the consultation of a general practitioner or consultant gives rise to worry about possible illness.

Cognitive behavioural therapy for medically unexplained physical symptoms: a randomised controlled trial.

OBJECTIVE: To examine the additional effect of cognitive behavioural therapy for patients with medically unexplained physical symptoms in comparison with optimised medical care. DESIGN: Randomised controlled trial with follow up assessments six and 12 months after the baseline evaluation. SETTING: General medical outpatient clinic in a university hospital. SUBJECTS: An intervention group of 39 patients and a control group of 40 patients. INTERVENTIONS: The intervention group received between six and 16 sessions of cognitive behavioural therapy. Therapeutic techniques used included identification and modification of dysfunctional automatic thoughts and behavioural experiments aimed at breaking the vicious cycles of the symptoms and their consequences. The control group received optimised medical care. MAIN OUTCOME MEASURES: The degree of change, frequency and intensity of the presenting symptoms, psychological distress, functional impairment, hypochondriacal beliefs and attitudes, and (at 12 months of follow up) number of visits to the general practitioner. RESULTS: At six months of follow up the intervention group reported a higher recovery rate (odds ratio 0.40; 95% confidence interval 0.16 to 1.00), a lower mean intensity of the physical symptoms (difference -1.2; -2.0 to -0.3), and less impairment of sleep (odds ratio 0.38; 0.15 to 0.94) than the controls. After adjustment for coincidental baseline differences the intervention and control groups also differed with regard to frequency of the symptoms (0.32; 0.13 to 0.77), limitations in social (0.35; 0.14 to 0.85) and leisure (0.36; 0.14 to 0.93) activities, and illness behaviour (difference -2.5; -4.6 to -0.5). At 12 months of follow up the differences between the groups were largely maintained. CONCLUSION: Cognitive behavioural therapy seems to be a feasible and effective treatment in general medical patients with unexplained physical symptoms.

Polymyalgia rheumatica and temporal arteritis: a retrospective study of 111 patients.

There is no unanimity as to whether polymyalgia rheumatica (PMR) and temporal arteritis (TA) are two distinct diseases or different features of one disease. The objective of this study was to assess the value of histological findings of temporal artery biopsy and the efficacy and complications of drug therapy as well as the frequency of malignancies. It was carried out as a retrospective follow-up study. One hundred eleven patients (89 PMR, 14 TA and 8 PMR+TA) were studied. In 56 patients with PMR a temporal artery biopsy was performed; in none of these biopsies was active arteritis found. Of the 19 patients with TA or PMR+TA, where a temporal artery biopsy was performed, arteritis was found in 15 patients. Reactivation occurred in 27 patients: 4 patients using NSAIDs and 23 patients using corticosteroids. Side effect of the medication included vertebral compression in 10 patients, most of whom were using corticosteroids. Malignancies were diagnosed in 12 of the 111 patients. Most malignancies were diagnosed long before or after the diagnosis of PMR. In case of a PMR diagnosed by the clinician a biopsy of the temporal artery has no value, while the yield of this diagnostic procedure is high in TA. Reactivation was seen quite often and warrants a prolonged period of medical treatment.

The acceptability of psychological treatment in patients with medically unexplained physical symptoms.

Patients with unexplained physical symptoms are considered to benefit from psychological treatment, but are believed to be reluctant to accept a referral to a psychiatrist or psychologist. As a part of a treatment study, we had the opportunity to examine to what extent somatising patients are willing to accept psychological treatment and how patients who are willing to accept it differ from those who are not. The study was introduced to the patient by the attending physician, and the treatment took place in the general medical outpatient clinic itself. Of 229 patients who had presented with unexplained physical symptoms to a general hospital medical outpatient clinic, 172 (75%) were interviewed at about three months after their initial visit to the clinic. Fourty-five (26%) patients appeared to have either improved or recovered from their presenting symptoms, and 26 (15%) were already receiving psychiatric or psychological treatment. Of 98 patients eligible for treatment, 79 (81%) were willing to participate. Compared with the patients who agreed to take part, the nonparticipants reported lower levels of physical symptoms and less functional impairment. In conclusion, most of the patients who might have benefitted from additional psychological help were willing to accept it. Somatising patients who rejected psychological treatment were those with the least serious problems.

Detecting psychiatric disorders in medical practice using the General Health Questionnaire. Why do cut-off scores vary?

In this study we assessed the accuracy of the General Health Questionnaire in detecting psychiatric disorders in general medical out-patients. A total of 290 newly referred patients were interviewed with the Present State Examination. Prior to the interview, 112 patients completed the full GHQ-60, 100 completed the GHQ-30 and 78 completed the GHQ-12. Data from the first group were used to study the full GHQ-60, together with the GHQ-30 and and GHQ-12, when disembedded from the full questionnaire. In a comparison between the disembedded and the separate versions of the GHQ-30 and GHQ-12 we observed considerable variation in the cut-off scores where a certain sensitivity and specificity was attained. In ROC-analysis, the versions were not materially different in their discriminatory capacity (area under the curve). The use of different criteria to define a 'case' demonstrated that case severity was another source of increasing cut-off scores. Our data demonstrate that the use of disembedded or separate versions of the questionnaire, together with variation in the case criteria can be a major explanation for variation in cut-off scores that was observed in previous studies.

Key symptoms in the detection of affective disorders in medical patients.

Psychiatric disorder in medical patients often goes undetected. In this study we have attempted to identify a minimum set of key symptoms from an extensive research interview [Present State Examination (PSE)] that might assist in the identification of psychiatric disorders among general medical patients. Stepwise logistic regression analysis was used to identify PSE-items that contributed most to the PSE-CATEGO classification of psychiatric disorders in 192 Dutch medical out-patients. A risk score based on two core symptoms (panic and depressed mood) and five supplementary symptoms classified patients with a sensitivity of 0.94 and a specificity of 0.91. In a separate U.K. sample of medical in-patients, consisting of 37 PSE cases and age and sex matched controls, the risk score yielded a sensitivity and specificity of 0.89 and 0.97 respectively. The results suggest that a few questions concerning psychiatric symptoms may facilitate the identification of the majority of patients with anxiety and depressive disorders in medical populations.