Physical activity in rheumatoid arthritis: relationship to cardiovascular risk factors, subclinical atherosclerosis, and disease activity.

Objective: To investigate associations between physical activity and risk factors for cardiovascular disease (CVD), subclinical atherosclerosis, and disease activity in patients with early and long-standing rheumatoid arthritis (RA).Method: This cross-sectional study included 84 patients with early and 37 with long-standing RA (disease duration, mean ± sd: 1.4 ± 0.4 and 16.3 ± 2.3 years, respectively). Physical activity was measured using a combined accelerometer and heart-rate monitor. Further assessments were disease activity (erythrocyte sedimentation rate, Disease Activity Score in 28 joints), functional ability (Health Assessment Questionnaire), risk factors for CVD (blood lipids, i.e. triglycerides, high-density lipoprotein, low-density lipoprotein; blood glucose, blood pressure, sleeping heart rate, waist circumference, body mass index, and body fat), and subclinical atherosclerosis (pulse-wave velocity, augmentation index, and carotid intima-media thickness).Results: Physical activity variables did not differ between patients with early and long-standing RA. However, 37% of the patients with early and 43% of those with long-standing RA did not reach the World Health Organization's recommended levels of moderate to vigorous physical activity (MVPA). In a final multiple regression model, adjusted for age, gender, disease duration, and activity monitor wear time, higher total physical activity was associated with lower body fat and higher functional ability. With the same adjustments, more time spent in MVPA was associated with lower high-density lipoprotein and lower sleeping heart rate.Conclusions: Physical activity was associated with more favourable risk factors for CVD. However, many patients were physically inactive, stressing the importance of promoting physical activity in RA.

Photodynamic therapy is more effective than imiquimod for actinic keratosis in organ transplant recipients: a randomized intraindividual controlled trial.

BACKGROUND: Actinic keratoses (AKs) in solid organ transplant recipients (OTRs) are difficult-to-treat premalignancies and comparison of topical therapies is therefore warranted. OBJECTIVES: In an intraindividual study to compare the efficacy and safety of field treatment with methyl aminolaevulinate photodynamic therapy (MAL-PDT) and imiquimod (IMIQ) for AKs in OTRs. METHODS: OTRs (n = 35) with 572 AKs (grade I-III) in two similar areas on the face, scalp, dorsal hands or forearms were included. All patients received one MAL-PDT and one IMIQ session (three applications per week for 4 weeks) in each study area according to randomization. Treatments were repeated after 2 months (IMIQ) and 3 months (PDT) in skin with incomplete AK response. Outcome measures were complete lesion response (CR), skin reactions, laboratory results and treatment preference. RESULTS: The majority of study areas received two treatment sessions (PDT n = 25 patients; IMIQ n = 29 patients). At 3 months after two treatments, skin treated with PDT achieved a higher rate of CR (AK I-III median 78%; range 50-100) compared with IMIQ-treated skin areas (median 61%, range 33-100; P < 0·001). Fewer emergent AKs were seen in PDT-treated skin vs. IMIQ-treated skin (0·7 vs. 1·5 AKs, P = 0·04). Patients developed more intense inflammatory skin reactions following PDT, which resolved more rapidly compared with IMIQ (median 10 days vs. 18 days, P < 0·01). Patient preference (P = 0·47) and cosmesis (P > 0·30) were similar for PDT and IMIQ. CONCLUSIONS: Compared with IMIQ, PDT treatment obtained a higher rate of AK clearance at 3-month follow-up and achieved shorter-lasting, but more intense, short-term skin reactions.

Diagnostic agreement and interobserver concordance with teledermoscopy referrals.

BACKGROUND: Malignant melanoma and non-melanoma skin cancers are among the fastest increasing malignancies in many countries. With the help of new tools, such as teledermoscopy referrals between primary health care and dermatology clinics, the management of these patients could be made more efficient. OBJECTIVE: To evaluate the diagnostic agreement and interobserver concordance achieved when assessing referrals sent through a mobile teledermoscopic referral system as compared to referrals sent via the current paper-based system without images. METHODS: The referral information from 80 teledermoscopy referrals and 77 paper referrals were evaluated by six Swedish dermatologists. They were asked to answer questions about the probable diagnosis, the priority, and a management decision. RESULTS: Teledermoscopy generally resulted in higher diagnostic agreement, better triaging and more malignant tumours being booked directly to surgery. The largest difference between the referral methods was seen for invasive melanomas. Referrals for benign lesions were significantly more often correctly resent to primary health care with teledermoscopy. However, referrals for cases of melanoma in situ were also incorrectly resent five times. The interobserver concordance was moderate with both methods. CONCLUSION: By adding clinical and dermoscopic images to referrals, the triage process for both benign and dangerous skin tumours can be improved. With teledermoscopy, patients with melanoma especially can receive treatment more swiftly.

Daylight-mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp: a randomized multicentre study.

BACKGROUND: Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated PDT is a simple and tolerable treatment procedure for PDT. Methyl aminolaevulinate (MAL)-PDT is approved for the treatment of thin or nonhyperkeratotic AKs on the face and scalp. However, thick AK lesions are often treated as well when present in the field-cancerized treatment area. OBJECTIVES: In a randomized multicentre study to evaluate efficacy of daylight-mediated PDT for different severity grades of AKs. METHODS: One hundred and forty-five patients with a total of 2768 AKs (severity grades I-III) of the face and scalp were randomized to either 1½ or 2½ h exposure groups. After application of a sunscreen (sun protection factor 20) and gentle lesion preparation, MAL was applied to the entire treatment area. Patients left the clinic immediately after application and exposed themselves to daylight according to randomization. Daylight exposure was monitored with a wrist-borne dosimeter. RESULTS: No difference in lesion response was found between the 1½ and 2½ h exposure group. The mean lesion response rate was significantly higher in grade I lesions (75·9%) than in grade II (61·2%) and grade III (49·1%) lesions (P < 0·0001). Most grade II (86%) and III AKs (94%) were in complete response or reduced to a lower lesion grade at follow-up. Large variations in response rate of grade II and III AKs were found between centres. No association was found between response rate and light dose in patients who received an effective light dose of > 3·5 J cm(-2). CONCLUSIONS: Daylight-mediated PDT of moderate to thick AKs was less effective than daylight-mediated PDT of thin AKs especially in some centres. However, nearly all thicker lesions (grades II and III) were reduced to a lower lesion grade at 3 months after a single treatment of daylight-mediated PDT.

Teaching peripheral nerve blocks for the head and neck area to dermatologists.

BACKGROUND: Peripheral nerve blocks in the head and neck region can be useful for a large number of surgical or otherwise painful procedures carried out by dermatologists. As anaesthesiologists cannot always be available to help dermatologists place nerve blocks in outpatient settings, training courses for these physicians are warranted. OBJECTIVES: To present a method of teaching nerve blocks for the face and scalp to dermatologists during residency and/or continuing medical education programmes. METHODS: Half-day courses with theoretical education, video demonstrations and supervised 'hands-on' training were organized to teach supraorbital/supratrochlear, infraorbital, mental and occipital nerve blocks. The outcome and effects of these training courses were analysed with a survey amongst participants 1-2 years after the course. RESULTS: All the 20 participants who responded the survey successfully placed at least one type of nerve block during the course. Thirteen of 20 participants (65%) reported to be able to perform all the nerve block techniques at follow-up. CONCLUSIONS: Dermatologists can learn how to perform nerve blocks for the face and scalp in a safe and controlled manner through half-day courses, including theory, video demonstrations and supervised 'hands-on' training.

A randomized, multicentre study of directed daylight exposure times of 1½ vs. 2½ h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp.

BACKGROUND: Actinic keratoses (AKs) are common dysplastic skin lesions that may differentiate into invasive squamous cell carcinomas. Although a superior cosmetic outcome of photodynamic therapy (PDT) is advantageous compared with equally effective treatments such as cryotherapy and curettage, the inconvenience of clinic attendance and discomfort during therapy are significant drawbacks. Daylight-mediated PDT could potentially reduce these and may serve as an alternative to conventional PDT. OBJECTIVES: To compare the efficacy of methyl aminolaevulinate (MAL)-PDT with 1½ vs. 2½ h of daylight exposure in a randomized multicentre study. METHODS: One hundred and twenty patients with a total of 1572 thin AKs of the face and scalp were randomized to either 1½- or 2½-h exposure groups. After gentle lesion preparation and application of a sunscreen of sun protection factor 20, MAL was applied to the entire treatment area. Immediately after, patients left the clinic and exposed themselves to daylight according to the randomization. Daylight exposure was monitored with a wristwatch dosimeter and patients scored their pain sensation during treatment. RESULTS: The mean lesion response rate at 3 months was 77% in the 1½-h group and 75% in the 2½-h group (P = 0·57). The mean duration of daylight exposure was 131 and 187 min in the two groups. The mean overall effective light dose was 9·4 J cm(-2) (range 0·2-28·3). Response rate was not associated with effective daylight dose, exposure duration, treatment centre, time of day or time of year during which the treatment was performed. Treatment was well tolerated, with a mean ± SD maximal pain score of 1·3 ± 1·5. CONCLUSIONS: Daylight-mediated MAL-PDT is an effective, convenient and nearly pain-free treatment for patients with multiple thin AKs. Daylight-mediated PDT procedures were easily performed and 2 h of daylight exposure resulted in uniformly high response rates when conducted in the period from June to October in Nordic countries.

Respiratory physiology at altitude.

The changes in respiratory physiology that occur with increasing altitude are driven by the fall in the partial pressure of oxygen that occurs with decreasing barometric pressure. At altitude, respiratory system changes occur which impact on each step of the oxygen cascade that occurs within the body. These changes are pivotal to the process of acclimatisation to altitude. The study of human respiratory physiology at altitude has the potential to produce research that will be translational to disease states characterised by hypoxaemia.

Nerve blocks enable adequate pain relief during topical photodynamic therapy of field cancerization on the forehead and scalp.

BACKGROUND: Topical photodynamic therapy (PDT) is an effective method when treating extensive areas of sun-damaged skin with multiple actinic keratoses (AKs) (field cancerization) on areas such as the forehead and scalp, and offers excellent cosmetic outcome. The major side-effect of PDT is the pain experienced during treatment. OBJECTIVES: To investigate whether nerve blocks could provide adequate pain relief during PDT of AKs on the forehead and scalp. METHODS: Ten men with symmetrically distributed and extensive AKs on the forehead and scalp were included in the study. Prior to PDT one side of the forehead and scalp was anaesthetized by nerve blocks while the other side served as control. RESULTS: The mean visual analogue scale (VAS) score on the anaesthetized side was 1 compared with 6.4 on the nonanaesthetized side during PDT. This difference was significant (P<0.0001), implying that nerve blocks reduce VAS scores during PDT. CONCLUSIONS: The results of the study support the use of nerve blocks as pain relief during PDT of field cancerization on the forehead and scalp, although individual considerations must be taken into account to find the most adequate pain-relieving method for each patient.

Bioavailability of aminolaevulinic acid and methylaminolaevulinate in basal cell carcinomas: a perfusion study using microdialysis in vivo.

BACKGROUND: Photodynamic therapy is becoming a popular treatment for superficial nonmelanoma precancerous and cancerous lesions, showing excellent cosmetic results. Nevertheless, the reported cure rates vary and the transdermal penetration of drugs has been discussed as a limiting factor, particularly for treatment of nodular basal cell carcinoma (BCC). OBJECTIVES: To investigate the transdermal penetration of aminolaevulinic acid (ALA) and methylaminolaevulinate (MAL) in BCC in vivo using a microdialysis technique. The different prodrugs were compared and the effect of curettage was studied. METHODS: Twenty patients with 27 histologically verified BCCs (13 superficial, 14 nodular) were included. All lesions were located at the front of the body (head and face excluded). The first 10 patients included were treated with MAL (13 BCCs), and the following 10 patients with ALA (14 BCCs). A light curettage was performed on every second lesion (curettage, n = 13; noncurettage, n = 14). Microdialysis catheters were inserted into the tumours at tissue depths varying from 0.4 to 1.9 mm. Dialysates were collected at 15-30-min intervals for 4 h and the interstitial concentrations of MAL and ALA were determined using high-performance liquid chromatography. RESULTS: No significant difference in interstitial drug concentration was observed between lesions treated with ALA or MAL during the 4-h measurement period. However, for the lesions with deeper catheter locations, i.e. at or below 1 mm (n = 11), drug concentrations above the detection limit were obtained in only six lesions. All but one BCC with superficial catheter location, i.e. < 1 mm (n = 16), exhibited detectable drug concentration (P = 0.026). The interstitial peak concentrations were reached within 90 min in 23 of the 27 BCCs, but were not found to be correlated with the depth of the catheters. No difference was found when comparing superficial and nodular BCCs, and the effect of curettage was found to be negligible. CONCLUSIONS: The results imply that there is no significant difference in transdermal penetration of ALA and MAL in tumour tissue. Detectable levels of drug were not obtained in almost 50% of the lesions where catheters were situated 1-1.9 mm in the lesion. Curettage was not found to affect the interstitial concentration, indicating that penetration of drug indeed might be a problem when treating BCCs thicker than 1 mm.

Bcl-XL protects pancreatic adenocarcinoma cells against CD95- and TRAIL-receptor-mediated apoptosis.

In this study we sought to clarify the role of the proapoptotic potential of mitochondria in the death pathway emanating from the TRAIL (APO-2L) and CD95 receptors in pancreatic carcinoma cells. We focused on the role of the Bcl-2 family member Bcl-XL, using three pancreatic carcinoma cell lines as a model system, two of which have high (Panc-1, PancTuI) and one has low (Colo357) Bcl-XL expression. In these cell lines, the expression of Bcl-XL correlated with sensitivity to apoptosis induced by TRAIL or anti-CD95. Flow cytometric analysis revealed cell surface expression of TRAIL-R1 and TRAIL-R2 on PancTuI and Colo357, and TRAIL-R2 on Panc-1 cells. In Colo357 cells retrovirally transduced with Bcl-XL, caspase-8 activation in response to treatment with TRAIL or anti-CD95 antibody was not different from parental cells and EGFP-transfected controls, however, apoptosis was completely suppressed as measured by the mitochondrial transmembrane potential deltapsim, caspase-3 activity (PARP cleavage) and DNA-fragmentation. Inhibition of Bcl-XL function by overexpression of Bax or administration of antisense oligonucleotides against Bcl-XL mRNA resulted in sensitization of Panc-1 cells to TRAIL and PancTuI cells to anti-CD95 antibody-induced cell death. The results show that Bcl-XL can protect pancreatic cancer cells from CD95- and TRAIL-mediated apoptosis. Thus, in these epithelial tumour cells the mitochondrially mediated 'type II' pathway of apoptosis induction is not only operative regarding the CD95 system but also regarding the TRAIL system.

Induction of a myocardial adrenomedullin signaling system during ischemic heart failure in rats.

BACKGROUND: Increased plasma adrenomedullin (ADM) levels have been reported in congestive heart failure (HF). The present study was designed to investigate myocardial regulation of the different components of the ADM signaling system (ADM, ADM receptor, and receptor-activity-modifying protein-2, RAMP-2) during ischemic HF in rats and to identify the cells in the myocardium displaying ADM-like immunoreactivity (ADM-ir). Furthermore, the effects of endothelin (ET) receptor antagonism on expression of the myocardial ADM system during HF were investigated. METHODS AND RESULTS: Northern blot analysis revealed increased ADM mRNA expression in the nonischemic left ventricle, with maximal levels 28 days after induction of myocardial infarction (1.5-fold, P<0.05) compared with the sham group. Parallel elevations of myocardial ADM receptor and RAMP-2 mRNA levels were also observed (2.3- and 1.5-fold increase, respectively; P<0.05). In addition, high levels of ADM mRNA were seen in the ischemic region. Immunohistochemical analysis revealed a substantial increase of ADM-ir in microvascular endothelium and perivascular interstitial cells of myocardial tissue contiguous to the ischemic region. In addition, radioligand binding studies demonstrated a 1.6-fold increase of specific ADM binding sites in the failing left ventricle (P<0.05). Intervention with the mixed ET(A)/ET(B) receptor antagonist bosentan (100 mg. kg(-1). day(-1) PO) for 15 days prevented the increase of RAMP-2 mRNA. CONCLUSIONS: The study demonstrates a concerted induction of several components of the myocardial ADM signaling system during postinfarction failure and that the vessels are the main source of myocardial ADM. Our observations indicate a role for ADM as an autocrine/paracrine factor during ventricular remodeling after myocardial infarction.

Disposition of methadone in methadone maintenance.

Six detoxified opiate addicts housed in a closed metabolic ward received methadone in stepwise increasing doses of 10, 20, 40, and 80 mg/day during 1 month. Four were given 14C-methadone at the lowest dose and again at the highest dose. Of the subjects receiving radiomethadone, 2 excreted the major part of the radioactivity in urine and 2 about equally in urine and feces. In addition to methadone, 7 metabolites were isolated and identified in urine and 3 metabolites in feces. About 75% of the urinary and fecal radioactive metabolites were unconjugated. Urinary excretion of methadone and its major N-monomethylated metabolite accounted for 17% to 57% of the given dose. The ratio of metabolite to parent drug increased in 5 of 6 subjects, and the urinary recovery of unchanged methadone decreased during the period. The results indicate that enhanced demethylation of methadone may occur during oral administration to man.

Separation of oxidized and deamidated human growth hormone variants by isocratic reversed-phase high-performance liquid chromatography.

Reversed-phase high-performance liquid chromatography (RP-HPLC) was utilized for the separation of recombinant human growth hormone (hGH) variants on a C18 silica column at 55 degrees C using an isocratic mobile phase which contained 27% 1-propanol in a 25 mM potassium phosphate buffer, pH 6.5. Three of the obtained peaks were characterized by tryptic mapping and mass spectrometry; two of the peaks were found to contain oxidized hGH (dioxy Met14/Met125 and Met125 sulfoxide) while the third contained a deamidated form (Asn149-->Asp149 or Asn152-->Asp152). Compared to the European Pharmacopoeia RP-HPLC method of hGH analysis, this new method gives two additional peaks and a 50% reduction in the analysis time.

Dilatation of the cervix prior to vacuum aspiration by single vaginal administration of 15-methyl-PGF2 alpha methyl ester.

PIP: The efficacy and safety of treatment with 1 vaginal suppository containing 15-methyl prostaglandin (PG) F2 alpha-methyl ester for cervical dilatation before vacuum aspiration in the 9th-14th week of pregnancy were tested in 489 patients: Group 1, patients 9-12 weeks pregnant, received a 1-mg suppository; Group 2, patients 13-14 weeks pregnant, were given a 1.5-mg dose. The vacuum aspiration procedure was performed 12 hours after insertion of the suppository. Mean cervical dilatation at the operation was 9.4 mm in Group 1 and 10.9 mm in Group 2. In about 50% of the patients, the cervix was further dilatated at operation. Mean additional dilatation was 2.8 and 1.5 mm, respectively, accomplished with minimum resistance. Mean bleeding at operation, including the conceptus, for the 9-12 week pregnant patients was 60 ml, and for Group 2, 135 ml. Gastrointestinal side effects, i.e., vomiting and diarrhea, were common but were rare only in cases frequent enough to be regarded as disturbing to the patient. No other treatment-requiring side effects were observed. In 22% of the patients in both treatment groups, the conceptus was expelled into the vagina prior to the operation. No cervical laceration was observed, and no uterine perforation occurred at the operation.^ieng

Drug-free treatment selection for chemical abusers: a diagnostic-based model.

The frequent treatment failures of patients with alcohol and drug-abuse disorders are often attributable to poor treatment choice. The absence from the literature of clinically relevant criteria for serving this population is noted. Four categories of patients are identified, and a diagnostic framework for the selection of drug-free treatments is proposed.

Biological correlates of social support and pressure at work in managers.

The aim was to explore the patterns of correlations between psychosocial stress indices and neuroendocrinological factors in managers. Fifty-eight male managers in three Swedish companies constituted the sample. They answered two questionnaires with 17 selected stress indices and also an organizational test. The indices have been analyzed by means of computations of age adjusted partial correlations with nine different variables analyzed in fasting blood samples. The serum concentrations of lipids were the variables most strongly correlated with psychosocial factors. Neither smoking nor physical activity changed the correlations significantly. Good social support at work and in private life was consistently associated with low adverse serum lipids and corresponding lipoproteins. On the other hand, some indices of social support were associated with indices of high arousal levels. This may indicate a possible psychophysiological "load effect" of some aspects of social support in managers. The analyses of corporate culture measured as "Rules of the Game" indicated that "bureaucracy" was significantly associated with high LDL-cholesterol and low HDL-cholesterol. Managers have special conditions and therefore the patterns of associations between psychosocial conditions and coping strategies on one hand and endocrine-biochemical state on the other hand may be different from those of other groups. To what extent such differences are due to individual characteristics or environmental factors needs to be further investigated. According to the results, however, good social support is in general health promoting also to managers, at least with regard to serum lipids. Bureaucracy, on the other hand, seems to be dangerous to the health of managers.

Telemedicine in Sweden--a diffusion study.

A survey of telemedicine use in Sweden was carried out. The response rate by hospital management was high at almost 90%. Sixty per cent of hospitals were involved in some kind of telemedicine activity in Sweden, with a further 15% planning telemedicine implementation. In rural areas of north Sweden good links exist between primary and secondary care. In the more populated southern region good links exist between the county hospitals and specialist university hospitals. Fifty-four per cent of telemedicine applications were used for specialist consultations, 13% for consultation between paramedics and hospitals and 10% for rounds. Teleradiology was the most frequent service.