Rosiglitazone for prevention or adjuvant treatment of Nelson's syndrome after bilateral adrenalectomy

OBJECTIVE: To investigate the effect of Rosiglitazone in three patients treated with bilateral adrenalectomy followed by hyperpigmentation and hypersecretion of ACTH. PATIENTS AND METHODS: One patient had increasing ACTH after previous transsphenoidal surgery for Nelson's syndrome, and two patients without pituitary adenomas had recurrence of Cushing's disease after primary and repeated transsphenoidal surgery with need for bilateral adrenalectomy. The patients developed hyperpigmentation and increasing ACTH at nadir 2-4 h after morning hydrocortisone dose. ACTH during Rosiglitazone therapy (4 mg/day for 4 weeks and then 8 mg/day) was measured at regular intervals 24 h after the latest dose of hydrocortisone. RESULTS: In two patients there was a decrease in ACTH by 40% after 5 months. The first of these patients showed an escape with increasing ACTH to the initial value after 11 months. In the third patient no effect was observed. Tumour development or progression on magnetic resonance imaging was not observed. CONCLUSION: Rosiglitazone might represent an adjuvant therapy in patients with ACTH hypersecretion. Larger long-term studies are needed.     

Occurrence and future history of oesophageal symptoms in an urban Swedish population: results of a questionnaire-based, ten-year follow-up study

OBJECTIVE: To evaluate the occurrence and changes over time of upper gastrointestinal symptoms in adult subjects randomly recruited from the general population. MATERIAL AND METHODS: A questionnaire recording of upper gastrointestinal symptoms with a 10-year follow-up was carried out in a random sample of the adult population of G?teborg. The original sample, from 1986, comprised 441 subjects within the age span of 20-79 years. In total, 337 subjects participated in the index assessment, of which 197 (95 F) subsequently answered the second questionnaire 10 years later. RESULTS: A majority of the responders (159/197, 83%) reported no change in their global assessment of symptoms. Neither the point prevalence nor the severity for any symptom changed significantly over time. The prevalence of heartburn and acid regurgitation was 25 and 22%, respectively, and the corresponding yearly incidence was estimated to be 1.8 and 1.2%. The main predictor for the occurrence of symptoms of moderate to severe degree at follow-up was the presence of the same symptom 10 years previously. Age or gender per se did not significantly influence the occurrence of symptoms. Changes in body mass index and anti-reflux medication co-varied with the severity of the symptoms heartburn and acid regurgitation. CONCLUSIONS: Oesophageal symptoms are common in the adult Swedish population and seem to be fairly stable over time.     

Cerebrospinal fluid interferon-gamma-inducible protein 10 (IP-10, CXCL10) in HIV-1 infection

Interferon-gamma-inducible protein (IP-10 or CXCL10) is a potent chemoattractant and has been suggested to enhance retrovirus infection and mediate neuronal injury. In order to assess this chemokine in central nervous system (CNS) HIV infection, we measured the cerebrospinal fluid (CSF) and plasma concentrations of CXCL10 by immunoassay in samples derived from 97 HIV-infected subjects across a spectrum of immunological progression and CNS complications and from 16 HIV seronegative control subjects studied at three clinical centers between 1994 and 2001. We also examined changes in the CSF and plasma CXCL10 concentrations in 30 subjects starting and three stopping antiretroviral therapy. CSF CXCL10 concentrations: (1) correlated with CSF HIV RNA and white blood cell (WBC) counts, but not with blood CXCL10, HIV RNA, or CD4 counts; (2) were increased in subjects with primary and asymptomatic HIV infections and AIDS dementia complex, but less frequently in those with more advanced infection, with or without CNS opportunistic diseases except cytomegalovirus encephalitis; (3) decreased in subjects starting antiretroviral in association with decreases in CSF and plasma HIV RNA and CSF WBCs; and (4) conversely, increased in subjects stopping treatment in parallel with CSF HIV RNA and WBCs. These results confirm that CSF CXCL10 associates closely with both CSF HIV and WBCs and suggest that this chemokine may be both a response to and contributing determinant of local infection. High CSF levels may be useful in the diagnosis of ADC in subjects with advanced immunosuppression in whom CMV encephalitis has been ruled out, though this issue requires further study.     

Seasonal variation in hospitalization and case fatality of subarachnoid hemorrhage - a nationwide danish study on 9,367 patients

Seasonal variation in the occurrence of cerebrovascular disease has been reported, but data about subarachnoid hemorrhage (SAH) are few and inconclusive. We conducted a nationwide population-based study in Denmark to examine any seasonal pattern of hospitalization and case fatality of SAH. We identified 9,367 patients with SAH and found a modest indication of overall seasonal variation for the risk of hospitalization with this diagnosis. The seasonal pattern, with the highest incidence in January and the nadir in July, was mostly apparent for subjects aged >65 years (peak-to-trough ratio = 1.18; 95% CI 1.04-1.32). There was little difference by sex. The overall 30-day case fatality rate was 38% and showed less seasonal variation. We found evidence of weak seasonal variation in hospitalization for SAH and almost no seasonal variation in a 30-day case fatality rate after SAH.     

Diagnostic stability in depressive disorder as according to ICD-10 in clinical practice

BACKGROUND: The diagnostic stability of the ICD-10 diagnosis of depressive disorder has not been investigated in clinical practice. SAMPLING AND METHODS: All patients who were diagnosed with depressive disorder at least once in a period from 1994 to 2002 in psychiatric out- or inpatient settings in Denmark were identified in a nationwide register. RESULTS: A total of 39,741 patients were diagnosed with depressive disorder at least once; among these, 81% were diagnosed at the first contact. In approximately 56% of patients, the initial diagnosis of depressive disorder eventually changed during follow-up mainly to the schizophrenic spectrum (16%), but also to personality disorders (9%), neurotic, stress-related and somatoform disorders (8%) and to bipolar disorder (8%). Among the 18% of patients who were later diagnosed with depressive disorder, 23% initially had a diagnosis of adjustment disorder. CONCLUSIONS: When the ICD-10 diagnoses are used in clinical practice, the diagnosis of depressive disorder has a low stability over time. These findings emphasize the need for a longitudinally based diagnostic process in the diagnostic systems.     

Coherence of EMG activity and single motor unit discharge patterns in human rhythmical force production

The purpose of this study was to examine the modulation of the motor neuronal pool as a function of task dynamics. Specifically, we investigated the effects of task frequency on the single motor unit discharge pattern, electromyogram (EMG) activity and effector force output. Myoelectric activity and effector force were recorded while young adults isometrically abducted their first dorsal interosseus at five sinusoidal targets (0.5 Hz, 1 Hz, 2 Hz, 3 Hz and 4 Hz) and at two force levels (5% and 25% maximum voluntary contraction (MVC)). Individual motor unit spike trains were isolated from the EMG. Auto-spectral and coherence analyses were performed on the force output, EMG and motor unit spike trains. The frequency of maximal coherence between the EMG and force output closely corresponded to the target frequency in all conditions. There was a broadband distribution of power with multiple peaks in the EMG and motor unit spectrums in the 0.5 Hz and 1 Hz targets. However, the EMG and motor unit spectrums in the 2 Hz, 3 Hz and 4 Hz targets were characterized by an increasingly narrower band of activity with one dominant peak that closely corresponded to the target. There is high coherence between EMG output and target force frequency, but the relative contribution of the fast and slow neuromuscular bands are differentially influenced by the task frequency. The rhythmical organization of neuromuscular output in the 0.5 Hz task is relatively broadband and similar to that shown previously for constant level force output. The frequency structure of neuromuscular organization becomes increasingly more narrowband as the frequency of the target increases (2-4 Hz). The modulation of the motor neuronal pool is adaptive and depends on the relative contribution of feedback and feedforward control processes, which are driven by the task demands.     

Coping with critical life events and lack of control--the exertion of control

Coping strategies in relation to unfair treatment or conflicts at work are discussed. ‘Covert coping’ has been assessed by means of a short questionnaire. Its relationship with cardiovascular risk and sick leave has been examined in an epidemiological study (WOLF) of working men and women in Stockholm. The findings indicate that in men ‘covert coping’ is associated with elevated cardiovascular risk and prospective long-term sick leave. In women such a coping strategy is related to current sick leave, but not to cardiovascular risk or long-term sick leave. Openness of coping strategies is also discussed in relation to bouts of anger preceding myocardial infarction. Another epidemiological study (SHEEP, ONSET) has shown that severe bouts of anger are reported significantly more often than expected during the hour preceding myocardial infarction. This was not the case in subjects who reported ‘open coping patterns’, however. Openness of coping strategies is partly determined by the working climate—the higher the decision latitude, the less ‘covert’ the coping strategies. The results support the idea that dialogue in the work place may be health promoting.     

Sex steroid-related genes and male-to-female transsexualism

Transsexualism is characterised by lifelong discomfort with the assigned sex and a strong identification with the opposite sex. The cause of transsexualism is unknown, but it has been suggested that an aberration in the early sexual differentiation of various brain structures may be involved. Animal experiments have revealed that the sexual differentiation of the brain is mainly due to an influence of testosterone, acting both via androgen receptors (ARs) and--after aromatase-catalyzed conversion to estradiol--via estrogen receptors (ERs). The present study examined the possible importance of three polymorphisms and their pairwise interactions for the development of male-to-female transsexualism: a CAG repeat sequence in the first exon of the AR gene, a tetra nucleotide repeat polymorphism in intron 4 of the aromatase gene, and a CA repeat polymorphism in intron 5 of the ERbeta gene. Subjects were 29 Caucasian male-to-female transsexuals and 229 healthy male controls. Transsexuals differed from controls with respect to the mean length of the ERbeta repeat polymorphism, but not with respect to the length of the other two studied polymorphisms. However, binary logistic regression analysis revealed significant partial effects for all three polymorphisms, as well as for the interaction between the AR and aromatase gene polymorphisms, on the risk of developing transsexualism. Given the small number of transsexuals in the study, the results should be interpreted with the utmost caution. Further study of the putative role of these and other sex steroid-related genes for the development of transsexualism may, however, be worthwhile.     

Amyloid-beta oligomers are inefficiently measured by enzyme-linked immunosorbent assay

Amyloid-beta (Abeta) peptide levels are widely measured by enzyme-linked immunosorbent assay (ELISA) in Alzheimer's disease research. Here, we show that oligomerization of Abeta results in underestimated Abeta ELISA levels. The implications are that comprehensive analysis of soluble Abeta requires either sample pretreatment at denaturing conditions or novel conformation-dependent immunoassays. Our findings might be of relevance for many neurodegenerative disorders in which soluble protein aggregates are the main neurotoxic species.