The burden of non-communicable diseases and mortality in people living with HIV (PLHIV) in the pre-, early- and late-HAART era.

OBJECTIVES: To estimate the burden of non-communicable diseases (NCDs) and mortality among PLHIV in the pre-, early- and late-HAART (highly active antiretroviral therapy) era. METHODS: We conducted a cohort study using population-based Danish medical registries including all adult HIV-infected residents of the Central Denmark Region during 1985-2017. For each HIV patient, we selected 10 comparisons from the background population matched by age, sex and municipality of residence. Based on hospital-related diagnoses we estimated the prevalence and incidence of specific NCD at diagnosis and at 5 and 10 years. RESULTS: We identified 1043 PLHIV and 10 430 matched comparisons. PLHIV had lower socioeconomic status and more were born outside western Europe. At HIV diagnosis, 21.9% of PHLIV vs. 18.2% of non-HIV individuals had at least one NCD, increasing to 42.2% vs. 25.9% after 10 years. PLHIV had higher prevalence and cumulative incidence of alcohol abuse, chronic obstructive pulmonary disease (COPD), ischaemic heart disease, mental disorders, renal and liver disease, but no increased risk of diabetes mellitus. Only PLHIV in the age groups 41-50 and > 51 years had an increased incidence of osteoporosis. From the pre- to the late-HAART era, 10-year mortality among PLHIV decreased from 45.5% to 9.4% but continued at more than twice that of uninfected comparisons. However, in the late-HAART era, the mortality of PLHIV who were alive 2 years after HIV diagnosis was approaching that of comparisons. CONCLUSIONS: Even in the late-HAART era, PLHIV have an excess mortality, which may be attributable to several NCDs being more prevalent among PLHIV. The prevalence rates of ischaemic heart disease, diabetes, osteoporosis and renal disease tend to increase over calendar time. Therefore, improvement of survival and quality of life of PLHIV neets strategies to reduce the risk of developing NCDs, including avoiding toxic antiretroviral therapy and lifestyle changes.

Identification and Characterization of a Nationwide Danish Adult Common Variable Immunodeficiency Cohort.

In this study, we identified all adults living in Denmark diagnosed with common variable immunodeficiency (CVID) and characterized them according to clinical presentation and EUROclass classification. Using a retrospective, cross-sectional design, possible CVID patients were identified in the Danish National Patient Register and Centers in Denmark treating patients with primary immunodeficiencies. The CVID diagnosis was verified by review of medical records. One-hundred-seventy-nine adults with CVID were identified. This corresponds to a prevalence of 1:26,000. The median age at onset of symptoms was 29 years with no sex difference. The median age at diagnosis was 40 years. Males were diagnosed earlier with a peak in the fourth decade of life, whereas females were diagnosed later with a peak in the sixth decade. The median diagnostic delay was seven years. Recurrent sinopulmonary infections were seen in 92.7% of the patients. The prevalence of non-infectious complications was similar to that of previously reported cohorts: bronchiectasis (35.8%), splenomegaly (22.4%), lymphadenopathy (26.3%), granulomatous inflammation (3.9%) and idiopathic thrombocytopenic purpura (14.5%). Non-infectious complications were strongly associated with B cell phenotype, with all having a reduced number of isotype-switched memory B cells. One-hundred-seventy (95%) were treated with immunoglobulin replacement therapy, primarily administered subcutaneously. According to international guidelines, diagnostic evaluation was inadequate in most cases. This study emphasizes the need for improved diagnostic criteria and more awareness of CVID as a differential diagnosis. Diagnosis and management of CVID patients is a challenge requiring specialists with experience in the field of PID.

Acute acalculous cholecystitis in a patient with primary Epstein-Barr virus infection: a case report and literature review.

Epstein-Barr Virus (EBV) infection can lead to infectious mononucleosis syndrome with the typical symptoms of fever, pharyngitis, and lymphadenopathy. Self-limited mild to moderate elevation of liver enzymes and hepatosplenomegaly are common. However, cholecystitis is not usually considered part of a primary EBV infection and ultrasound scan (USS) of the liver and gallbladder is not routinely performed. Acute acalculous cholecystitis (AAC) caused by etiologies other than primary EBV infection is often associated with severe illness and antibiotic treatment and surgery may be needed. We present a case with primary EBV infection and AAC and a literature review. Our patient was a 34-year-old woman with clinical, biochemical and serological signs of primary EBV infection (lymphocytes 7.6×10˄9/l, monocytes 2.6×10˄9/l, positive early antigen IgM test and 14 days later positive early antigen IgG test). During admission, increasing liver function tests indicated cholestasis (alanine aminotransferase 61 U/l, alkaline phosphatase 429 U/l and bilirubin 42µmol/l). USS revealed a thickened gallbladder wall indicating cholecystitis but no calculus. All other microbiological tests were negative. The literature search identified 26 cases with AAC and acute EBV infection; 25 cases involved females. Sore throat was not predominant (six reported this), and all cases experienced gastrointestinal symptoms. Our and previous published cases were not severely ill and recovered without surgical drainage. In conclusion primary EBV infection should be considered in cases of AAC, especially in young women. In cases associated with EBV infection neither administration of antibiotics nor surgical drainage may be indicated.

Utilization of psychotropic drugs prescribed to persons with and without HIV infection: a Danish nationwide population-based cohort study.

OBJECTIVES: The objective was to estimate the utilization of psychotropic drugs in HIV-infected individuals compared with that in the background population. METHODS: Using data obtained from the Danish HIV Cohort Study and the Danish National Prescription Registry, we analysed aggregated data on redeemed prescription of psychotropic drugs during 1995-2009. We primarily focused our analyses on HIV-infected individuals with no history of injecting drug use (IDU) or hepatitis C virus (HCV) infection. Drug utilization was expressed as defined daily doses per 1000 person-days (DDD/1000PD). The utilization rate ratio (URR) was calculated as utilization in the HIV-infected cohort compared with that in the comparison cohort. We estimated longitudinal trends in utilization and potential associations with HIV and exposure to highly active antiretroviral therapy (HAART), especially efavirenz. RESULTS: During 1995-2009, 54.5% of the HIV-infected cohort (3615 non-IDU/non-HCV-infected HIV-infected individuals) and 29.2% of the comparison cohort (32 535 individuals) had at least one prescription of a psychotropic drug. HIV infection was associated with a URR of 1.13 for antipsychotics, 1.76 for anxiolytics, 4.42 for hypnotics and sedatives, and 2.28 for antidepressants. Antidepressants were confined primarily to men who have sex with men (MSM). Older age, more recent calendar time, and increased time after HIV diagnosis were associated with increased drug utilization. However, no association with exposure to HAART or efavirenz was found. CONCLUSIONS: HIV-infected individuals had a higher utilization of psychotropic drugs than the background population, which was not confined to individuals with a history of IDU or HCV infection. This emphasizes the need to focus on diagnosis of, and appropriate psychopharmacological interventions for, mental disorders in this population.

No change in viral set point or CD4 cell decline among antiretroviral treatment-naïve, HIV-1-infected individuals enrolled in the Danish HIV Cohort Study in 1995-2010.

OBJECTIVES: Recent studies have reported faster progression of HIV infection than anticipated based on results from earlier studies. The aim of the present study was to examine if the virulence of HIV-1 infection changed in the period 1995-2010 among chronically HIV-infected individuals in Denmark. METHODS: We included all patients registered in the Danish HIV Cohort Study, who were diagnosed in 1995-2009, had a CD4 count > 100 cells/µL at diagnosis and had at least two CD4 measurements prior to initiation of antiretroviral therapy (ART). Changes in viral set point and rate of CD4 cell decline from enrolment until the initiation of ART by calendar year of HIV diagnosis were analysed. Time to first CD4 count < 350 cells/µL was compared among patients diagnosed in 1995-2000, 2001-2005 and 2006-2010. RESULTS: We followed 1469 HIV-infected patients for a total of 5783 person-years. The median viral set point was 4.27 log10 HIV-1 RNA copies/mL [interquartile range (IQR) 3.58-4.73 log10 copies/mL]. The median CD4 cell decline per year was 57 cells/µL (IQR 10-139 cells/µL). In analyses adjusted for age, gender, origin, route of transmission and CD4 count at diagnosis, there were no associations between year of diagnosis and viral set point or CD4 cell decline. Time to first CD4 count < 350 cells/µL did not change in the study period [incidence rate ratio (IRR) 0.90 (95% confidence interval (CI) 0.76-1.06) for 2001-2005 and 1.09 (95% CI 0.79-1.34) for 2006-2010 compared with 1995-2000]. CONCLUSIONS: We found no evidence of changing trends in viral set point, CD4 cell decline or time to CD4 count < 350 cells/µL during the period 1995-2010 in a cohort of chronically HIV-infected individuals.

Causes of death among Danish HIV patients compared with population controls in the period 1995-2008.

PURPOSE: To compare the mortality and causes of death in human immunodeficiency syndrome (HIV) patients with the background population. METHODS: All adult HIV patients treated in Danish HIV centers from 1995 to 2008 and 14 controls for each HIV patient were included. Age-adjusted mortality rates (MR) and mortality rate ratios (MRR) were estimated using direct standardization and Poisson regression analyses. Up to four contributory causes of death for each person were included in analyses of cause-specific MR. RESULTS: A total of 5,137 HIV patients and 71,918 controls were followed for 37,838 and 671,339 person-years (PY), respectively. Among non-injection drug use (IDU) HIV patients, the acquired immune deficiency syndrome (AIDS)-related MR/1,000 PY declined dramatically from 122.9 [95 % confidence interval (CI) 106.8-141.4] in 1995 to 5.0 (95 % CI 3.1-8.1) in 2008. The non-AIDS-related MR did not change substantially from 6.9 (95 % CI 3.8-12.5) to 5.6 (95 % CI 3.6-8.8). The MR of unnatural causes declined from 6.9 (95 % CI 3.8-12.5) to 2.7 (95 % CI 1.4-5.1). The MRR of infections declined from 46.6 (95 % CI 19.6-110.9) to 3.3 (95 % CI 1.6-6.6). The MRR of other natural causes of death remained constant. CONCLUSIONS: After the introduction of highly active antiretroviral therapy (HAART), the AIDS-related mortality has decreased substantially, but the long-term exposure to HIV and HAART has not translated into increasing mortality from malignancy, cardiovascular, and hepatic diseases.

Major but differential decline in the incidence of Staphylococcus aureus bacteraemia in HIV-infected individuals from 1995 to 2007: a nationwide cohort study*.

OBJECTIVES: Incidence rates (IRs) of Staphylococcus aureus bacteraemia (SAB) are known to be higher in HIV-infected individuals than in the general population, but have not been assessed in the era of highly active antiretroviral therapy. METHODS: From 1 January 1995 to 31 December 2007, all Danish HIV-infected individuals (n=4871) and population controls (n=92 116) matched on age and sex were enrolled in a cohort and all cases of SAB were registered. IRs and risk factors were estimated using time-updated Poisson regression analysis. RESULTS: We identified 329 cases of SAB in 284 individuals, of whom 132 individuals were infected with HIV and 152 were not [crude IR ratio (IRR) 24.2; 95% confidence interval (CI) 19.5-30.0, for HIV-infected vs. non-HIV-infected individuals]. Over time, IR declined for HIV-infected individuals (IRR 0.40). Injecting drug users (IDUs) had the highest incidence and the smallest decline in IR, while men who have sex with men (MSM) had the largest decline over time. Among HIV-infected individuals, a latest CD4 count <100 cells/µL was the strongest independent predictor of SAB (IRR 10.2). Additionally, HIV transmission group was associated with risk of SAB. MSM were more likely to have hospital-acquired SAB, a low CD4 cell count and AIDS at the time of HIV acquisition compared with IDUs. CONCLUSIONS: We found that the incidence of SAB among HIV-infected individuals declined during the study period, but remained higher than that among HIV-uninfected individuals. There was an unevenly distributed burden of SAB among HIV transmission groups (IDU>MSM). Low CD4 cell count and IDU were strong predictors of SAB among HIV-infected individuals.

HIV and risk of venous thromboembolism: a Danish nationwide population-based cohort study.

OBJECTIVE: The association between HIV infection and the risk of venous thromboembolism (VTE) is controversial. We examined the risk of VTE in HIV-infected individuals compared with the general population and estimated the impact of low CD4 cell count, highly active antiretroviral therapy (HAART) and injecting drug use (IDU). METHODS: We identified 4333 Danish HIV-infected patients from the Danish HIV Cohort Study and a population-based age- and gender-matched comparison cohort of 43,330 individuals. VTE diagnoses were extracted from the Danish National Hospital Registry. Cumulative incidence curves were constructed for time to first VTE. Incidence rate ratios (IRRs) and impact of low CD4 cell count and HAART were estimated by Cox regression analyses. Analyses were stratified by IDU, adjusted for comorbidity and disaggregated by overall, provoked and unprovoked VTE. RESULTS: The 5-year risk of VTE was 8.0% [95% confidence interval (CI) 5.78-10.74%] in IDU HIV-infected patients, 1.5% (95% CI 1.14-1.95%) in non-IDU HIV-infected patients and 0.3% (95% CI 0.29-0.41%) in the population comparison cohort. In non-IDU HIV-infected patients, adjusted IRRs for unprovoked and provoked VTE were 3.42 (95% CI 2.58-4.54) and 5.51 (95% CI 3.29-9.23), respectively, compared with the population comparison cohort. In IDU HIV-infected patients, the adjusted IRRs were 12.66 (95% CI 6.03-26.59) for unprovoked VTE and 9.38 (95% CI 1.61-54.50) for provoked VTE. Low CD4 cell count had a minor impact on these risk estimates, while HAART increased the overall risk (IRR 1.93; 95% CI 1.00-3.72). CONCLUSION: HIV-infected patients are at increased risk of VTE, especially in the IDU population. HAART and possibly low CD4 cell count further increase the risk.

Abacavir and risk of myocardial infarction in HIV-infected patients on highly active antiretroviral therapy: a population-based nationwide cohort study.

OBJECTIVE: The aim of the study was to examine whether exposure to abacavir increases the risk for myocardial infarction (MI). DESIGN, SETTING AND SUBJECTS: This was a prospective nationwide cohort study which included all Danish HIV-infected patients on highly active antiretroviral therapy (HAART) from 1995 to 2005 (N = 2952). Data on hospitalization for MI and comorbidity were obtained from Danish medical databases. Hospitalization rates for MI after HAART initiation were calculated for patients who used abacavir and those who did not. We used Cox's regression to compute incidence rate ratios (IRR) as a measure of relative risk for MI, while controlling for potential confounders (as separate variables and via propensity score) including comorbidity. MAIN OUTCOME: Relative risk of hospitalization with MI in abacavir users compared with abacavir nonusers. RESULTS: Hospitalization rates for MI were 2.4/1000 person-years (PYR) [95% confidence interval (CI) 1.7-3.4] for abacavir nonusers and 5.7/1000 PYR (95% CI 4.1-7.9) for abacavir users. The risk of MI increased after initiation of abacavir [unadjusted IRR = 2.22 (95% CI 1.31-3.76); IRR adjusted for confounders = 2.00 (95% CI 1.10-3.64); IRR adjusted for propensity score = 2.00 (95% CI 1.07-3.76)]. This effect was also observed among patients initiating abacavir within 2 years after the start of HAART and among patients who started abacavir as part of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen. CONCLUSIONS: We confirmed the association between abacavir use and increased risk of MI. Further studies are needed to control for potential confounding not measured in research to date.

Changing demographics in an HIV-infected population: results from an observational cohort study in Western Denmark.

We present demographic data from an observational database of HIV and AIDS in the Western part of Denmark, a region with a population of 2,935,156 individuals (55.1% of the population of Denmark). Five centers in the region treat HIV-positive adults; all patients attached to these centers since 1995 are included in this study. In total, 749 adult HIV-infected individuals were enrolled as of 31 December, 1999. Estimates of prevalence and incidence of HIV infection in the area were 25.9/100,000 and 2.6/100,000, respectively, which are lower than average for the country. The number of newly diagnosed HIV-infected patients remained constant during the period 1995-99, with an average of 62 diagnoses per year. The number of HIV-related deaths declined from 43 in 1995 to 15 in 1999. Of the enrolled patients, 70.9% were of Danish origin, 75% were Caucasians, 69.7% were male and 47.2% had heterosexual contact as their primary risk behavior. There seems to have been a shift in the HIV epidemic in recent years, with a higher proportion of newly diagnosed HIV patients having contracted the infection through heterosexual contact, a higher proportion being immigrants from less developed countries and newly diagnosed individuals getting older.

Effects of subcutaneous IL-2 therapy on telomere lengths in PBMC in HIV-infected patients.

In this study we investigated the effect of interleukin-2 (IL-2) on mean terminal restriction fragment (TRF) lengths in peripheral blood mononuclear cells (PBMC). Ten human immunodeficiency virus (HIV)-infected individuals were included and IL-2 was administered subcutaneously with 3 x 106 IU three times a week for 24 weeks. Mean TRF length was decreased on average by 267 bp at week 4 (P = 0.03) and 286 bp at week 8 (P = 0.09). Individual TRF changes at weeks 12, 16, 20 and 24 were highly variable. However, in the 12 weeks following therapy, TRF lengths generally increased reaching baseline levels by the end of the study. At baseline, mean TRF lengths were positively correlated to the ratio of naïve and memory phenotype within both CD4+ and CD8+ cells. This study shows that IL-2 treatment induces transient shortened mean TRF lengths in PBMC from HIV-infected individuals, indicating that IL-2 enhances the lymphocyte count by peripheral proliferation or recruitment of memory T cells into the blood.

Subcutaneous interleukin-2 in combination with anti-retroviral therapy for treatment of HIV-1-infected subjects.

A total of 11 HIV-1 positive patients, with CD4+ cell counts between 200 and 500/microl, who were in stable anti-retroviral therapy, were treated with subcutaneous recombinant human IL-2 thrice weekly administered on an out-patient basis in a dose-escalating manner. Subcutaneous IL-2 was well tolerated and associated with only mild to moderate constitutional symptoms and local inflammation at the injection site. CD4+ cell count increased from 404 +/- 48/microl at baseline to 639 +/- 88/microl at week 6, with proportionate increases in naive cells and memory cells. Increased doses of IL-2 were then needed to sustain the number of CD4+ cells. After discontinuation of IL-2 treatment, CD4+ cell count returned to baseline levels. IL-2 induced a reduction in the percentage of CD8+ CD38+ and CD8+ HLA-DR+ cells, an increase in the fraction of CD8+ CD25+ and CD8+ CD122+, and an elevation in the number of NK-cells. IL-2 did not induce any clinically significant change in plasma HIV-RNA. In conclusion, IL-2 can safely be administered subcutaneously on an out-patient basis to HIV-infected individuals with CD4+ cell counts from 200/microl to 500/microl and with some improvement in immunological abnormalities. Continuous therapy, however, seems to result in the development of tachyphylaxia.

Effects of subcutaneous interleukin-2 therapy on phenotype and function of peripheral blood mononuclear cells in human immunodeficiency virus infected patients.

In the context of clinical therapy with recombinant human interleukin-2 (IL-2), we monitored immunological alteration in 10 human immunodeficiency virus type-I (HIV-1)-infected individuals, on stable antiretroviral therapy, who had a CD4+ cell count between 200 and 500 cells/mm3. Subcutaneous IL-2 was prescribed thrice weekly (at a dose of 3 x 10(6) IU) for 24 weeks and the patients were followed-up for 32 weeks. IL-2 treatment induced an increase in the CD4+ percentage (P<0.001) and CD4+ cell count (P<0.009). Furthermore. natural killer (NK) cell activity was increased (P<0.001) at week 8 of treatment, whereas lymphokine-activated killer (LAK) cell activity showed a transient, nonsignificant increase at week 8 and was reduced (P<0.001) at 32 weeks. However, the cytotoxic T-lymphocyte (CTL) activity decreased against HIV antigens, and the proliferative response to Candida, IL-2 and phytohaemagglutinin (PHA) declined during the first 8 weeks (P<0.05) and returned to baseline levels after 32 weeks. The HIV RNA level did not change during IL-2 therapy; however, after 8 weeks of follow-up a significant increase (P<0.001) in viral load was observed. In

Elemental signatures of human diets from the Georgia Bight.

Multielement analysis was performed on bone samples extracted from the femora of 39 adults from three mortuary sites (Johns Mound, Santa Catalina de Guale, and Santa Catalina de Guale de Santa Maria) and time periods (late preagricultural, early contact, and late contact) in the Georgia Bight. This study was used to investigate whether elemental analysis would support or contradict other lines of data regarding diets and dietary change previously generated for the region. The data are in agreement with an earlier interpretation, based on stable isotopes, that dietary maize increases through time but fails to support the idea that marine resources decreased in importance. Rather, it appears that the wild plant food component of the diets decreases as maize increases in importance; throughout the sequence, marine resources comprise a significant portion of the diets.

Postcranial robusticity in Homo. I: Temporal trends and mechanical interpretation.

Temporal trends in postcranial robusticity within the genus Homo are explored by comparing cross-sectional diaphyseal and articular properties of the femur, and to a more limited extent, the humerus, in samples of Recent and earlier Homo. Using both theoretical mechanical models and empirical observations within Recent humans, scaling relationships between structural properties and bone length are developed. The influence of body shape on these relationships is considered. These scaling factors are then used to standardize structural properties for comparisons with pre-Recent Homo (Homo sp. and H. erectus, archaic H. sapiens, and early modern H. sapiens). Results of the comparisons lead to the following conclusions: 1) There has been a consistent, exponentially increasing decline in diaphyseal robusticity within Homo that has continued from the early Pleistocene through living humans. Early modern H. sapiens are closer in shaft robusticity to archaic H. sapiens than they are to Recent humans. The increase in diaphyseal robusticity in earlier Homo is a result of both medullary contraction and periosteal expansion relative to Recent humans. 2) There has been no similar temporal decline in articular robusticity within Homo--relative femoral head size is similar in all groups and time periods. Thus, articular to shaft proportions are different in pre-Recent and Recent Homo. 3) These findings are most consistent with a mechanical explanation (declining mechanical loading of the postcranium), that acted primarily through developmental rather than genetic means. The environmental (behavioral) factors that brought about the decline in postcranial robusticity in Homo are ultimately linked to increases in brain size and cultural-technological advances, although changes in robusticity lag behind changes in cognitive capabilities.

Carbon and nitrogen stable isotopic signatures of human dietary change in the Georgia Bight.

Measurement of carbon and nitrogen stable isotope ratios (delta 13C and delta 15N) in samples of human bone collagen (n = 93) from a temporal series of four prehistoric (early preagricultural, late preagricultural, early agricultural, late agricultural) and two historic (early contact, late contact) periods from the Georgia Bight, a continental embayment on the southeastern U.S. Atlantic coast, reveals a general temporal trend for less negative delta 13C values and less positive delta 15N values. This trend reflects a concomitant decrease in emphasis on marine resources and increased reliance on C4-based resources, especially maize. This dietary reorientation is most apparent for the early agricultural sample (AD 1150-1300), coinciding with the Mississippian fluorescence in the eastern United States. There is, however, a shift toward the use of C3 (non-maize) foods during the last prehistoric period (AD 1300-1450), which is likely related to environmental stress and social disruption. A heavier use of maize and terrestrial resources in general after the establishment of mission centers on barrier islands is indicated. A reduced dietary breadth during the mission period may have contributed to the extinction of these populations in the eighteenth century.

Monocyte chemotactic activity in sera after hypnotically induced emotional states.

In a number of studies it has been shown that psychological factors in general and specifically emotional factors can be correlated to changes in immunological function and defence mechanisms. Although the mediating pathways between the central nervous system and the immune system still remain unclear, it is known that some of the 'classical stress hormones' such as cortisol and catecholamines have modulatory effects on different immunological parameters. In this investigation we wished to study the effect of brief hypnotically induced emotional states on monocyte chemotaxis and endocrinological parameters. Eleven highly hypnotically susceptible volunteers were, while in a deep trance, given suggestions to re-experience earlier life experiences involving intense anger and depression in random order. Before concluding hypnosis subjects were given suggestions to re-experience a feeling of happiness and well-being. Monocyte chemotactic activity in sera and serum levels of cortisol, as well as venous plasma levels of the catecholamines epinephrine, norepinephrine, DOPA and DOPAC, were measured before hypnosis, after each emotional state and immediately after hypnosis. The results showed a significant differences (P less than 0.02) in chemotactic activity between the angry and the depressed emotional states, the depressed state exhibiting a decreased chemotactic index compared with the angry state. Chemotactic index after the happy relaxed emotional state also showed a significant (P less than 0.01) increase compared with both chemotactic index before hypnosis and chemotactic activity after the angry and depressed state. Though there were significant differences between emotions and between emotions and the before-hypnosis-condition, no clear-cut significant differences between the emotional states of anger and depression could be detected for serum cortisol levels and catecholamine plasma levels. Significant positive correlations (P less than 0.01) for differences in chemotactic activity and differences in plasma DOPA levels between emotional states was found. When investigated in vitro, DOPA did not in itself exhibit monocyte chemotactic properties. No other significant correlations between differences in chemotactic activity and other endocrinological parameters could be detected. Soluble interleukin-2 receptors in serum were also measured. No significant differences were found.

Soluble IL2 receptor serum levels and epidermal cytokines in mycosis fungoides and related disorders.

We examined the immune activation in 20 patients with mycosis fungoides, 6 patients with erythrodermia of unknown origin (Pré-Sézary's syndrome), 5 with lymphomatoid papulosis, 4 with parapsoriasis, 2 with Sézary's syndrome, and 2 with actinic reticuloid, by measuring soluble interleukin-2 receptor levels in serum. In Mycosis fungoides we observed normal levels in 3 patients (less than 500 units/ml), between 500 and 1000 units/ml in 9 patients, and greater than 1000 units/ml in 5 patients. Four of these 5 patients died within one year after this observation, as did 2 patients with Pré-Sézary and Sézary's syndrome, respectively, who had a similarly large increase in sIL2R. Although sIL2R is not a specific parameter for cutaneous T-cell lymphoma, a value above 1000 units/ml is correlated with clinical disease activity and is a serious prognostic parameter. We also studied cytokine activity in epidermal homogenates from 9 patients with Mycosis fungoides and one patient with Sézary's syndrome. We observed interleukin-1-like activity within the normal range for healthy skin. However, we also observed in the same epidermal homogenates a T-lymphocyte chemotactic activity in patients with stage II, but not in stage I. The nature of this activity is not yet fully elucidated, but it may be an important biological factor for the epidermal T-cell accumulation in this disorder.