Detection of molecular variants of prolactin in human serum, evaluation of a method based on ultrafiltration

BACKGROUND: In human blood, there are several molecular variants of prolactin with different biological effects. There is a need for new methods to detect and quantify these variants in order to fully understand the pathophysiological role of prolactin. METHODS: A method based on ultrafiltration was optimized, validated and compared to PEG precipitation. Serum samples from 84 patients were analyzed before and after pre treatment on two immunoassays, Elecsys (Roche) and Access (Beckman). Protein G precipitation was used to confirm presence of macroprolactin. RESULTS: The recovery of prolactin after ultrafiltration was lower than after PEG precipitation. A limit of 40% recovery after PEG precipitation corresponded to 27% recovery after ultrafiltration. Using these limits there were total agreement regarding detection of macroprolactin (r(s)=0.96). In contrast, recovery of prolactin in samples without macroprolactin showed a considerable disagreement between ultrafiltration and PEG precipitation (r(s)=0.48). Within-run CV was 4% for the ultrafiltration method. The correlation coefficient (r) between the immunoassays was 0.96 after ultrafiltration. CONCLUSIONS: Ultrafiltration can be used to compare different prolactin immunoassays and to detect macroprolactin in assays with interference from PEG. For samples without macroprolactin ultrafiltration may give additional information reflecting individual variations of other molecular variants of prolactin.     

Adacolumn,an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes

Apheresis has been recognized both economically and therapeutically as a novel approach for the treatment of inflammatory diseases, and certain others, which respond poorly to drug therapy. This report is about Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device with a volume of 335 mL, filled with about 220 g of cellulose acetate beads of 2 mm diameter as the column adsorptive carriers. Pre- and post-column leukocyte counts have shown that the carriers adsorb about 65% of granulocytes, 55% of monocytes and 2% of lymphocytes from the blood in the column. Additionally, after apheresis, there is a marked decrease in inflammatory cytokines (TNF-alpha, IL-1beta, IL-6 and IL-8) produced by blood leukocytes, together with down-modulation of L-selectin and the chemokine receptor CXCR3. Adacolumn has been used to treat patients with rheumatoid arthritis, ulcerative colitis and HIV infection. Typical apheresis sessions have been 4-10, at a frequency of one or two sessions per week. Treatment of patients with Adacolumn has been associated with very promising efficacy and safety data. Accordingly, in Japan, Adacolumn has been approved by the Ministry of Health for the treatment of ulcerative colitia. Furthermore, Adacolumn met the required quality and safety standards for medical devices and received an EC certification (CE-mark) from TUV in 1999. However, although Adacolumn carriers are very efficient in depleting excess and activated granulocytes and monocytes/macrophages, the clinical efficacy associated with Adacolumn apheresis cannot be fully explained on the basis of reducing granulocytes and monocytes per se. Hence, a long lasting effect on inflammatory cytokine generation, chemokine activities or immunomodulation is likely, but the precise mechanisms involved are not fully understood yet.     

Work Control, Work Demands, and Work Social Support in Relation to Alcoholism Among Young Men

Objectives : The aim of the study was to estimate the impact of psychosocial work-environment factors, such as low work control, on alcoholism among young men. Methods : Data on circumstances during childhood and adolescence, such as on risk use of alcohol, were collected for 49,323 young men, born 1949 to 1951 at time of enlistment for compulsory military training in 1969/1970. On the basis of census data on occupation in 1975, all individuals were classified into groups with regard to psychosocial work-environment factors in accordance with a job-exposure matrix. Follow-up for alcoholism diagnoses from inpatient care registers (1976 to 1983) was undertaken for each of the groups. A number of potential confounding factors were taken into account. Results : Low work control and also low job demands and low workplace social support were found to be related to later alcoholism. On separate analysis, the pattern among blue-collar workers was found to be similar to that of the entire population. When the analyses were extended to include indicators of risk use of alcohol and other relevant background factors, the relative risks decreased, but were still significantly high in the cases of low work control and low work social support. A combination of low demands and low control, what might be called a "passive" work environment, was related to an increased relative risk of psychiatric alcoholism diagnosis after controlling for relevant background factors. Conclusions : Low work control, in particular in combination with low work demands, and low work social support are related to later alcoholism even after controlling for previously known risk factors (including risk use of alcohol). The results suggest that young men may respond to an undemanding occupational environment by increasing their alcohol consumption.     

Dissatisfied patients after total knee arthroplasty: A registry study involving 114 patients with 8–13 years of follow-up

Background and purpose

In 2003, an enquiry by the Swedish Knee Arthroplasty Register (SKAR) 2–7 years after total knee arthroplasty (TKA) revealed patients who were dissatisfied with the outcome of their surgery but who had not been revised. 6 years later, we examined the dissatisfied patients in one Swedish county and a matched group of very satisfied patients.

Patients and methods

118 TKAs in 114 patients, all of whom had had their surgery between 1996 and 2001, were examined in 2009–2010. 55 patients (with 58 TKAs) had stated in 2003 that they were dissatisfied with their knees and 59 (with 60 TKAs) had stated that they were very satisfied with their knees. The patients were examined clinically and radiographically, and performed functional tests consisting of the 6-minute walk and chair-stand test. All the patients filled out a visual analog scale (VAS, 0–100 mm) regarding knee pain and also the Hospital and Anxiety and Depression scale (HAD).

Results

Mean VAS score for knee pain differed by 30 mm in favor of the very satisfied group (p < 0.001). 23 of the 55 patients in the dissatisfied group and 6 of 59 patients in the very satisfied group suffered from anxiety and/or depression (p = 0.001). Mean range of motion was 11 degrees better in the very satisfied group (p < 0.001). The groups were similar with regard to clinical examination, physical performance testing, and radiography.

Interpretation

The patients who reported poor response after TKA continued to be unhappy after 8–13 years, as demonstrated by VAS pain and HAD, despite the absence of a discernible objective reason for revision.The results of TKA are regarded as being favorable (Robertsson et al. 2000, Kane et al. 2005, Nilsdotter et al. 2009, Carr et al. 2012) with few surgical complications and a revision rate of less than 5% after 10 years (Vessely et al. 2006, Robertsson et al. 2010). Poor outcome after primary TKA, apart from the revision, is between 6% and 14% (Anderson et al. 1996, Hawker et al. 1998, Heck et al. 1998, Robertsson et al. 2000, Robertsson and Dunbar 2001, Brander et al. 2003, Noble et al. 2006, Fisher et al. 2007, Wylde et al. 2008, Kim et al. 2009, Bourne et al. 2010, Scott et al. 2010). The reason for poor outcome after TKA may be related to problems with the knee surgery itself, although it has been suggested that extra-articular causes such as hip disease, spine disorder, vascular disease, or reflex sympathetic dystrophy may contribute. Some studies have suggested that factors not primarily related to structural tissue changes, but of psychological nature instead, may be involved (Wylde et al. 2007, Rolfson et al. 2009).The Swedish Knee Arthroplasty Register (SKAR) registers primary arthroplasties performed in Sweden as well as revisions, and has been estimated to capture 97% of the surgeries performed (SKAR 2012). The SKAR sends questionnaires regarding satisfaction to patients who were operated on during certain time periods (Robertsson et al. 2000, and Dunbar 2001). We used the SKAR to identify patients who had not undergone revision surgery and who were dissatisfied with their outcome 2–7 years after TKA surgery. As a reference we chose an age-, sex-, date-of-surgery-, and hospital-matched control group of highly satisfied patients who were operated during the same period. Our aim was to assess the differences between these 2 patient groups.     

Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk for future surgery for aortic stenosis

Abstract

Recently, a new approach was proposed to detect mild impairment in renal function: a reduced ratio between estimated glomerular filtration rate (eGFR) calculated by cystatin C and eGFR calculated by creatinine. We aimed to evaluate if this ratio is associated with aortic stenosis (AS) requiring surgery. We identified 336 patients that first participated in population surveys and later underwent surgery for AS (median age [interquartile range] 59.8 [10.3] years at survey and 68.3 [12.7] at surgery, 48% females). For each patient, two matched referents were allocated. Cystatin C and creatinine were determined in stored plasma. eGFR_{cystatin C} and eGFR_creatinine and their ratio were estimated. Conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval (CI)]) related to one (ln) standard deviation increase in the ratio between eGFR_{cystatin C} and eGFR_creatinine. A high ratio was associated with lower risk for AS requiring surgery (OR [95% CI]) (OR 0.84 [0.73–0.97]), especially in women (0.74 [0.60–0.92] vs. 0.93 [0.76–1.13] in men). After further stratification for coronary artery disease (CAD), the association remained in women with CAD but not in women without CAD (0.60 [0.44–0.83] and 0.89 [0.65–1.23], respectively). In conclusion, a high ratio between eGFR_{cystatin C} and eGFR_creatinine was associated with lower risk for surgery for AS, especially in women. Mild impairment of renal function is thus associated with future risk for AS requiring surgery.     

Wound management for 287 patients with chronic leg ulcers demands 12 full-time nurses Leg ulcer epidemiology and care in a well-defined population in southern Sweden

Objective. To investigate quality of life, measured by the SF-36 scales, in a population-based sample of women who have survived cancer at any site and, specifically, breast cancer. Design. A representative cohort of women was observed over 24 years with regard to cancer prevalence, incidence, and quality of life. Setting. Gothenburg, Sweden. Subjects. A total of 1462 women aged 38–60 years at baseline. Main outcome measures. Differences in quality of life between cancer survivors and cancer-free controls measured by the SF-36 Short Form Health Survey, with adjustment for age and additionally for social status, and history of major disease (diabetes, stroke, and myocardial infarction) at follow-up in 1992–93. Results. In women who had survived cancer, a lower feeling of general health was the only score found to be significantly associated with having had cancer. Similar analysis was conducted separately for breast cancer cases. Survivors of breast cancer reported lower vitality and when controlled for major disease also lower general health compared with women who had not had cancer. All other results were independent when adjusted for social status, and also for history of major disease. Conclusions. Women who have survived cancer report lowered general health, and breast cancer cases lowered vitality, but considering the non-significant results for the other scores and summary scales it can be concluded that the well-being of women who have survived a cancer on the whole did not differ profoundly from that of other women.