Raynaud's phenomenon and its impact on activities in daily life during one year of follow-up in early systemic sclerosis.

OBJECTIVE: To investigate Raynaud's phenomenon (RP) and its impact on daily life activities during 1 year of follow-up in early systemic sclerosis (SSc). METHOD: Fourteen SSc patients with a median disease duration of 2 years were enrolled in the study. Every 7 weeks the patients completed a 7 day diary documenting the frequency and duration of RP attacks, the activity causing the attack, and how they handled the attack. The patients also recorded in the diary daily self-assessments of the difficulties with RP, using a 0-10 ordinal scale according to the Raynaud's Condition Score. RESULTS: Ninety-eight RP weekly diaries were analysed. The median number of RP attacks varied between six and nine per week, and the median score reflecting the difficulty associated with the attacks varied between 2.0 and 2.9. No difference was found in the number of attacks or the difficulties associated with them between winter, spring, and autumn. Fewer attacks and less difficulty were reported in August than in any of the other documented weeks (p < 0.05). In all diaries, all patients reported RP attacks associated with domestic activities. The use of heating devices varied during the follow-up. In February, all patients except one used such devices, while about half of the group used devices during the rest of the year. CONCLUSIONS: Difficulties resulting from RP are present and disabling all year round, which underscore the importance of intense vasoactive therapy and non-pharmacological strategies throughout the year.

Progressive capillary loss over a decade in patients with systemic sclerosis, in particular in patients with early digital ischaemic manifestations.

OBJECTIVE: Characteristic capillary abnormalities occur early in systemic sclerosis (SSc). Our aim was to study the longitudinal development of capillary density in SSc patients. METHODS: Forty-eight consecutive patients with SSc fulfilling a follow-up of at least 8 years were retrospectively analysed for capillary loss over the observation period. Eleven had diffuse cutaneous SSc (dcSSc) and 37 limited cutaneous SSc (lcSSc). The median disease duration at first assessment was 2.5 years. Capillary density was determined by direct counting of capillaries in the distal row on eight fingers in a stereo-zoom microscope at 20× magnification. RESULTS: Capillary density decreased over the observation period in dcSSc (from median 5.1 to 4.4 loops/mm, p < 0.05) and in lcSSc (from 5.1 to 4.2 loops/mm, p < 0.001). No significant difference was found between the two forms at start or at follow-up. Digital ischaemic manifestations had already been found at the first assessment in 19 patients. They did not differ in capillary density from those without ischaemic manifestations at the first assessment (5.0 and 5.3 loops/mm), but did differ at follow-up (3.6 and 4.7 loops/mm, p < 0.001). Capillary loss was more pronounced in patients who already had digital ischaemic manifestations at the first assessment compared to those without (p < 0.02). CONCLUSION: In SSc, early digital ischaemic manifestations may precede a subsequent progressive capillary loss. The association between capillary loss and serious internal vascular complications remains to be studied.

Survival in patients with pulmonary arterial hypertension associated with systemic sclerosis from a Swedish single centre: prognosis still poor and prediction difficult.

OBJECTIVES: To describe the survival rate in a cohort of systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) and to evaluate possible predictors for SSc-PAH in a cohort of SSc patients. METHODS: Thirty patients with SSc-PAH and 150 SSc patients without PAH were included. Survival and survival on therapy were calculated. Clinical features at baseline were correlated to the risk for development of PAH during follow-up. RESULTS: The 1-, 2-, 3-, and 4-year survival rates were 86, 59, 39, and 22%, respectively, from diagnosis of PAH. The hazard ratio for total mortality in the SSc-PAH group was 3.2 [95% confidence interval (CI) 1.8-5.7] compared to SSc without PAH (p < 0.001). Risk factors at baseline for the development of PAH were: limited skin involvement, low diffusing capacity of the lung for carbon monoxide (DL(CO)), high N-terminal pro-brain natriuretic peptide (NTProBNP), increased estimated systolic pulmonary arterial pressure (ESPAP), and the presence of teleangiectases. Severe peripheral vascular disease requiring iloprost treatment during follow-up was associated with an eightfold increased risk of PAH. CONCLUSION: Despite modern treatment and yearly screening by echocardiography, the survival in SSc-PAH is still low in our cohort. The identified risk factors should be assessed to select patients eligible for right heart catheterization (RHC) to make an earlier diagnosis.

Evaluación prospectiva de pacientes con SDRA con sospecha de infección por influenza a H1N1 en terapia intensiva. Seguimiento a los 30 días del alta / Prospective evaluation of patients with ARDS with suspected H1N1 influenza infection in intensive therapy. Follow-up 30 days after discharge

El objetivo del presente es la caracterización de pacientes en terapia intensiva en el hospital de alta complejidad, y portadores de insuficiencia respiratoria aguda con requerimiento de asistencia ventilatoria mecánica, a su vez, el comportamiento de pacientes con infección por el virus influenza H1N1 que desarrollan síndrome de dificultad respiratorio agudo (SDRA).

High-frequency ultrasound of skin involvement in systemic sclerosis reflects oedema, extension and severity in early disease.

OBJECTIVE: The aim was to compare skin assessment by palpation and by high-frequency ultrasound in patients with SSc with disease duration <2 yrs. METHODS: Skin thickness and skin echogenicity were measured by 20 MHz ultrasound at five different anatomical sites in 106 individuals within 2 yrs from the first non-Raynaud's symptom and compared with the modified Rodnan skin score (mRss). RESULTS: The patients with short disease duration were characterized by high skin thickness and low skin echogenicity, which correlated inversely, reflecting oedema. Patients with diffuse skin involvement displayed higher skin thickness and lower skin echogenicity than did patients with limited skin involvement. The ultrasound measurements correlated to the local mRss from the corresponding anatomical region and also to the total mRss. However, there was a considerable overlap in both skin thickness and skin echogenicity between different local mRss at all five anatomical sites. Skin involvement of the chest could be detected earlier by ultrasound than by palpation. CONCLUSION: In SSc patients with short disease duration, high-frequency ultrasound can identify the oedematous phase that may precede palpable skin involvement and may thus be useful to identify patients with diffuse skin involvement very early in the disease process. Ultrasound measurements also reflect the severity of the overall skin involvement.

Simple counting of nailfold capillary density in suspected systemic sclerosis - 9 years' experience.

OBJECTIVES: Capillary damage is a characteristic feature of systemic sclerosis (SSc). This work aimed to explore the potential clinical value of simple microscopic counting of capillary density. METHODS: In 325 patients admitted because of a clinical suspicion of SSc and in 80 healthy controls, nailfold capillary microscopy (NCM) was performed using a stereo-zoom microscope in 20 x magnification and with a transparent ruler in one of the eyepieces. Capillaries were counted within 3 mm in the centre of the nailfold in eight fingers. RESULTS: Capillary density (loops/mm) was decreased in patients with diffuse cutaneous SSc [median 4.7 (range 2.2-7.3)], limited cutaneous SSc [4.9 (2.0-7.3)], earlySSc [4.7 (2.8-7.3)], and preSSc [5.9 (4.3-8.2)] compared to healthy controls [7.2 (5.8-9.0)]. Patients with morphea and with primary Raynaud's phenomenon had normal numbers of capillaries [7.0 (6.2-7.2) and 7.0 (5.3-8.7), respectively]. In only 21/325 (6%) patients was it not possible to count the capillaries because of insufficient transparency of the skin. There was no discrepancy in capillary density based on counts of two or eight fingers. When 43 patients were reassessed after 1 to 4 years, there was no difference between the two assessments. CONCLUSION: Determination of capillary density by direct microscopy counts, a simple, inexpensive and rapid method, helps to identify patients with SSc, early in the disease course and in patients with very limited skin involvement.

BALF-derived fibroblasts differ from biopsy-derived fibroblasts in systemic sclerosis.

Growth of fibroblasts from bronchoalveolar lavage fluid (BALF) in patients with systemic sclerosis (SSc) has previously been described. The purpose of the present study was to characterise fibroblasts from BALF and bronchial biopsies from SSc patients with alveolitis and from controls, to analyse fibroblast proliferation, migration, stress fibres and proteoglycan production. BALF and bronchial biopsies were collected from 10 patients with SSc and alveolitis and from 15 controls. Outgrowth of fibroblasts was observed from the BALF of four patients, particularly in those with a markedly increased percentage of eosinophils in BALF, but not in any member of the control group. Increased levels of granulocyte-macrophage colony-stimulating factor, correlating with the percentage of eosinophils in BALF, were found in patients when compared with controls. Fibroblasts from BALF showed an elongated, mobile phenotype and increased proteoglycan production compared to the corresponding biopsy fibroblasts. In conclusion, outgrowth of fibroblasts with an altered phenotype is reported from bronchoalveolar lavage fluid in systemic sclerosis patients with alveolitis and an increased percentage of eosinophils in the bronchoalveolar lavage fluid. These findings indicate a possible role for eosinophil-fibroblast interaction in pulmonary fibrosis in systemic sclerosis.

Regulation of serotonin levels by multiple light-entrainable endogenous rhythms.

This study examined whether serotonin levels in the brain of the American lobster, Homarus americanus, are under circadian control. Using high-performance liquid chromatography and semi-quantitative immunocytochemical methods, we measured serotonin levels in the brains of lobsters at six time points during a 24-h period. Lobsters were maintained for 2 weeks on a 12 h:12 h light:dark cycle followed by 3 days of constant darkness. Under these conditions, brain serotonin levels varied rhythmically, with a peak before subjective dusk and a trough before subjective dawn. This persistent circadian rhythm in constant darkness indicates that serotonin levels are controlled by an endogenous clock. Animals exposed to a shifted light cycle for >10 days, followed by 3 days in constant darkness, demonstrate that this rhythm is light entrainable. Separate analyses of two pairs of large deutocerebral neuropils, the accessory and olfactory lobes, show that serotonin levels in these functionally distinct areas also exhibit circadian rhythms but that these rhythms are out of phase with one another. The olfactory and accessory lobe rhythms are also endogenous and light entrainable, suggesting the presence of multiple clock mechanisms regulating serotonin levels in different brain regions.

Longitudinal development of skin involvement and reliability of high frequency ultrasound in systemic sclerosis.

BACKGROUND: Measurement of skin involvement is essential for diagnosis and prognosis in systemic sclerosis. Assessment by palpation skin score is the current method. OBJECTIVE: To explore high frequency ultrasound as an objective method to improve skin characterisation by combining measurements of skin thickness and echogenicity. METHODS: Skin thickness and echogenicity were measured at the proximal phalanx of the second digit, the back of the hand, the forearm, and the lower leg and, in order to separate limited (lSSc) from diffuse SSc (dSSc), at the chest in 16 patients with early disease and in 16 controls. Measurements were repeated in each patient three or four times with an interval of 1-2 years. Ultrasound measurements of skin thickness were compared with the palpation skin score. RESULTS: Compared with controls, the skin was thickened on the phalanx, hand, forearm, and chest of patients with dSSc, but not patients with lSSc, at the 1 year examination. In dSSc the degree of thickening tended to diminish with time, and at 4 years, thickness was significantly decreased on the forearm and chest compared with the 1 year measurements. Low reflectancy was most pronounced at the 1 year evaluation on the forearm, hand, and phalanx in dSSc, and on the phalanx in lSSc. CONCLUSION: Separate measurements of skin thickness and echogenicity by high frequency ultrasound add a new dimension to the assessment of skin involvement in SSc, and this seems to be an objective non-invasive tool for use in the study of disease development and in clinical trials.

The association between changes in skin echogenicity and the fibroblast production of biglycan and versican in systemic sclerosis.

OBJECTIVE: To investigate a possible association between the longitudinal changes in skin involvement and the fibroblast production of proteoglycans in vitro, among patients with early and untreated systemic sclerosis (SSc). METHODS: In 11 patients, 6 with diffuse cutaneous systemic sclerosis (dSSc) and 5 with limited cutaneous systemic sclerosis (ISSc), and in 6 controls skin thickness and skin echogenicity of the forearm was measured by high frequency (20 MHz) ultrasound. A skin biopsy was taken from the area of the ultrasound measurements, and from cultivated fibroblasts the production of the proteoglycans versican, perlecan, biglycan and decorin were measured. To investigate longitudinal changes in skin involvement, the ultrasound examination was repeated after 1-3 years. RESULTS: Compared to controls, SSc patients had increased skin thickness at the first evaluation. Patients with dSSc had lower skin echogenicity than both patients with lSSc and the controls. Patients with greater changes in skin thickness and skin echogenicity produced more versican, whereas the production of biglycan and decorin was higher only in patients with greater changes in skin echogenicity. There was a negative correlation between fibroblast production of biglycan and disease duration. CONCLUSION: High fibroblast synthesis of the proteoglycans versican and biglycan is associated with changes in skin echogenicity and may predict more progressive skin sclerosis in SSc.

EAU Guidelines on benign prostatic hyperplasia (BPH).

OBJECTIVE: To establish guidelines for the diagnosis, treatment, and follow-up of BPH. METHODS: A search of published work was conducted using Medline. In combination with expert opinions recommendations were made on the usefulness of tests for assessment and follow-up: mandatory, recommended, or optional. In addition, indications and outcomes for the different therapeutic options were reviewed. RESULTS: A digital rectal examination is mandatory in the assessment for the diagnosis of BPH. Recommended tests are the International Prostate Symptom Score, creatinine measurement (or renal ultrasound), uroflowmetry, and postvoid residual urine volume. All other tests are optional. The aim of treatment is to improve patients' quality of life, and it depends on the severity of the symptoms of BPH. The watchful waiting policy is recommended for patients with mild symptoms, medical treatment for patients with mild-moderate symptoms, and surgery for patients who failed medication or conservative management and who have moderate-severe symptoms, and/or complications of BPH which require surgery. Regarding non-surgical treatments, transurethral microwave thermotherapy is the most attractive option. These treatments should be reserved for patients who prefer to avoid surgery or who no longer respond favourably to medication. Finally, recommendations for follow-up tests and a recommended follow-up time schedule after BPH treatment are provided. CONCLUSIONS: Recommendations for assessment, possible therapeutic options, and follow-up of patients with BPH are made.

Von Willebrand factor propeptide as a marker of disease activity in systemic sclerosis (scleroderma).

In 44 consecutive patients with systemic sclerosis (SSc), plasma concentrations of von Willebrand factor (vWf) were higher than those of the vWf propeptide, but the propeptide showed less variability within patient subgroups. Higher values of the propeptide were observed in patients with early pulmonary involvement. A closer correlation of the propeptide than of vWf to biochemical markers of activity was also evident. Our results suggest that the propeptide, despite a shorter circulating half-time and lower plasma concentrations than vWf, is more useful in the assessment of disease activity in SSc.

Clinical results of microwave thermotherapy for benign prostatic hyperplasia.

Transurethral microwave thermotherapy is a truly office procedure without the need for anesthesia for the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia. Several devices have been developed. Continuous refinement of the procedure led to higher energy protocols and high-intensity dose protocols applying the heat-shock strategy. We report on the clinical results of these protocols. Symptom scores improve around 60%, whereas maximum urinary flow rate improve from an average 9 to 10 mL/sec at baseline to 14 to 15 mL/sec during follow-up. No significant differences have been shown between the outcomes with the different devices. Long-term data show satisfactory results after 4 years. Initial clinical results with the heat-shock strategy show results comparable to those of higher-energy protocols with decreased morbidity. Treatment morbidity of higher energy protocols is moderate and consists mainly of the need for catheterization and a higher percentage of retrograde ejaculation. To improve treatment efficacy, patient selection appears to be most important. Prostate size, bladder outlet obstruction, age, and prostate composition are of predictive value for treatment outcome. Further development of the treatment protocols and refinement of the urethral applicators might enhance outcome.

Circulating collagen metabolites in systemic sclerosis. Differences between limited and diffuse form and relationship with pulmonary involvement.

OBJECTIVE: To study collagen metabolites in systemic sclerosis (SSc) and their relationship with clinical manifestations of the disease. METHODS: Forty-eight SSc patients, 13 with a diffuse form (dcSSc), 23 with a limited form (lcSSc) and 12 with suspected SSc not fulfilling the ACR criteria, and 31 healthy controls were examined. Serum concentrations of aminoterminal type III procollagen peptide (PIIINP), aminoterminal and carboxyterminal type I procollagen peptides (PINP and PICP) and cross-linked carboxyterminal telopeptide of collagen I (ICTP) were determined by radioimmunoassay. RESULTS: Increased serum concentrations of ICTP were found in SSc patients compared with controls. Distinctly higher levels of ICTP were observed in dcSSc than in lcSSc. High serum ICTP was correlated with skin score and acute phase reactants, and with reduced pulmonary function. Serum PIIINP concentration was elevated in both lcSSc and dcSSc. CONCLUSION: Augmented collagen catabolism accompanies the increased collagen synthesis in SSc. Serum ICTP concentration is a marker of this feature and also reflects clinical severity.

Decreased capillary density in juvenile dermatomyositis and in mixed connective tissue disease.

OBJECTIVE: To assess whether quantitative capillary microscopy is a useful tool to evaluate capillary abnormalities in children with connective tissue diseases. METHODS: Eight children with juvenile dermatomyositis (JDM), 6 with mixed connective tissue disease (MCTD) and 23 healthy children were investigated with computer based quantitative capillary microscopy. Median disease duration was 1 year among JDM (1-4) and 3 years (1-7) among MCTD. RESULTS: Capillary density was decreased in JDM [median 2.5 (1.4-4.3) loops/mm (p < 0.001)] and in MCTD [median 5.0 (4.1-7.0) loops/mm (p < 0.05)] compared to healthy controls [median 6.8 (5.3-8.0) loops/mm]. Median capillary loop area was increased in JDM [median 8.5 (3.0-15.8) 10(-3) mm2 (p < 0.001)] and in MCTD [median 4.5 (3.0-6.0) 10(-3) mm2 (p < 0.02)] compared to controls [median 2.5 (1.0-4.0) 10(-3) mm2]. CONCLUSION: Quantitative nailfold capillary microscopy is a sensitive indicator of JDM. In MCTD this technique is less discriminative.

Capillary density in patients with systemic sclerosis, as determined by microscopy counts and compared with computer-based analysis.

OBJECTIVE: To develop a method enabling capillary density to be determined rapidly and accurately in patients with systemic sclerosis. METHOD: Capillary density was determined in 11 controls and 22 patients: 5 with diffuse cutaneous systemic sclerosis (dSSc), 12 with limited cutaneous systemic sclerosis (lSSc), two with suspected systemic sclerosis (suspSSc), 2 with sclerodermatomyositis, and one with undifferentiated connective tissue disease. Using a microscope equipped with a graticule, nailfold capillaries were counted within a 3 mm length of the nailfold; these counts were made by 4 different observers. The results were compared with the corresponding values obtained by the computerbased analysis of photographs. RESULTS: The median capillary density according to the direct counts was 8.0 loops/mm (6.7-10.0) in the controls, 6.0 loops/mm (range 4.8-8.8) in the dSSc subgroup, 5.6 loops/mm (4.2-6.5) in the lSSc subgroup, and 7.2 loops/mm (6.2-8.2) in the suspSSc subgroup. In the series as a whole, there was no significant difference between the median values for the left hands and those for the right hands, nor between the median value for all digit IVs and the median value for all four digits analysed (II, III, IV, and V). Interobserver variation was small between the 4 different observers. Direct microscopy counts were slightly higher than the corresponding values obtained by computer-based analysis. CONCLUSION: Direct microscopy counting is a rapid, simple, and reliable means of determining capillary density for screening purposes.

Three-year followup of patients treated with lower energy microwave thermotherapy.

PURPOSE: A retrospective study was done to investigate the long-term outcome of patients treated with lower energy transurethral microwave thermotherapy. MATERIALS AND METHODS: A total of 305 patients with lower urinary tract symptoms and benign prostatic hypertrophy underwent transurethral microwave thermotherapy according to a similar protocol at 2 centers. RESULTS: After 3 years of followup 133 patients who had undergone transurethral microwave thermotherapy alone were available for study. During this observation period significant symptomatic improvement from baseline and an improved maximum flow rate of 2.6 ml. per second were noted. Of the patients 125 underwent invasive or medical treatment. CONCLUSIONS: After 3 years of followup lower energy transurethral microwave thermotherapy showed significant and durable improvements in baseline parameters in 52% of the patients.

Pressure-flow study analyses in patients treated with high energy thermotherapy.

PURPOSE: We evaluated the urodynamic changes after high energy microwave thermotherapy in patients with lower urinary tract symptoms and benign prostatic enlargement. MATERIALS AND METHODS: A total of 120 patients was available for analysis with urodynamic investigation and pressure-flow studies before and 6 months after treatment. Several obstruction parameters were used to evaluate treatment outcome. RESULTS: A significant decrease (p < 0.001) in all obstruction parameters was noted. Mean detrusor pressure at maximum flow decreased from 64.7 to 39.1 cm. water, urethral resistance factor from 41.8 to 23.5 cm. water and linear passive urethral resistance relation from 3.0 to 1.4. Analysis of subgroups showed better results in patients with greater degrees of obstruction. CONCLUSIONS: High energy thermotherapy results in a significant and substantial decrease in bladder outlet obstruction.