Management of opioid-induced constipation in pregnancy: a concise review with emphasis on the PAMORAs.

WHAT IS KNOWN AND OBJECTIVE: Opioid-induced constipation (OIC) is one of the most common opioid-induced adverse effects. Pregnancy also predisposes to bowel dysfunctions due to the associated endocrine changes. Pregnant women are thus at greater risk of OIC. We review the non-pharmacologic and pharmacologic treatment options as a guide for achieving a clinically optimal strategy for the management of OIC during pregnancy. METHODS: The published literature was searched for current therapeutic options, including non-pharmacologic dietary modifications, laxatives, and the peripherally acting mu-opioid receptor antagonists (PAMORAs). Each was assessed for efficacy and safety, particularly as they relate to pregnancy. RESULTS AND DISCUSSION: Non-pharmacologic approaches such as dietary change are generally safe, but generally insufficient when used alone to control OIC in pregnancy. Laxatives (bulking, osmotic, stimulant) can be effective, but have potential adverse effects that might be particularly troublesome during pregnancy (e.g. electrolyte disturbances, dehydration, abdominal pain, and pulmonary oedema or hypermagnesaemia in the extreme). PAMORAs, which attenuate OIC without affecting opioid-induced analgesia, have been associated with only minimal side effects during the clinical studies to date. WHAT IS NEW AND CONCLUSIONS: Conventional non-pharmacologic and pharmacologic options for the management of OIC in pregnancy are often suboptimal due to insufficient efficacy or adverse effects particularly troublesome during pregnancy. The PAMORA strategy appears to provide a safe and effective new option superior to conventional therapies for the management of OIC during pregnancy.

Correlations between nailfold microangiopathy severity, finger dermal thickness and fingertip blood perfusion in systemic sclerosis patients.

OBJECTIVE: The aim of this study was to identify possible correlations between nailfold microangiopathy severity, finger dermal thickness (DT) and fingertip blood perfusion (FBP) in systemic sclerosis (SSc) patients. METHODS: Fifty-seven SSc patients and 37 healthy subjects were enrolled. All patients were evaluated by nailfold videocapillaroscopy (NVC) to classify and score the severity of microangiopathy. Both modified Rodnan skin score (mRss) and skin high-frequency ultrasound were used to detect finger DT. Laser Doppler flowmetry (LDF) was employed to detect FBP. RESULTS: A positive correlation was found between nailfold microvascular damage severity and both ultrasound-DT (p=0.028) and mRss values (p<0.0001). In particular, both ultrasound-DT and mRss were found progressively higher in patients with 'Early', 'Active' or 'Late' NVC pattern of microangiopathy. A negative correlation was observed between nailfold microvascular damage severity and FBP (p<0.0001), showing the lowest FBP of the patients with more advanced NVC patterns. A negative correlation was observed between FBP, and both ultrasound-DT (p=0.007) and mRss values (p=0.0002). SSc patients showed a higher ultrasound-DT at the level of the fingers, as well as a lower FBP than healthy subjects (p<0.0001). CONCLUSIONS: This study demonstrates a relationship between nailfold microangiopathy severity, DT and FBP in SSc patients.

Unstable flow structures in the Blasius boundary layer.

Finite amplitude coherent structures with a reflection symmetry in the spanwise direction of a parallel boundary layer flow are reported together with a preliminary analysis of their stability. The search for the solutions is based on the self-sustaining process originally described by Waleffe (Phys. Fluids 9, 883 (1997)). This requires adding a body force to the Navier-Stokes equations; to locate a relevant nonlinear solution it is necessary to perform a continuation in the nonlinear regime and parameter space in order to render the body force of vanishing amplitude. Some states computed display a spanwise spacing between streaks of the same length scale as turbulence flow structures observed in experiments (S.K. Robinson, Ann. Rev. Fluid Mech. 23, 601 (1991)), and are found to be situated within the buffer layer. The exact coherent structures are unstable to small amplitude perturbations and thus may be part of a set of unstable nonlinear states of possible use to describe the turbulent transition. The nonlinear solutions survive down to a displacement thickness Reynolds number Re * = 496 , displaying a 4-vortex structure and an amplitude of the streamwise root-mean-square velocity of 6% scaled with the free-stream velocity. At this Re* the exact coherent structure bifurcates supercritically and this is the point where the laminar Blasius flow starts to cohabit the phase space with alternative simple exact solutions of the Navier-Stokes equations.

Seronegative spondyloarthritis and Darier's disease: more than a casual association?

A 46-year old man, affected by Darier's disease (DD), was seen because of right hand pain, later extended to shoulders and ankles. Physical examination showed swelling and tenderness of the wrist, metacarpophalangeal and metatarsophalangeal joints, of the right Achilles tendon's enthesis and of the left knee, with psoriatic-like lesions of the scalp. A diagnosis of seronegative spondyloarthritis, supported by HLA-B27 positivity and by the magnetic resonance imaging finding of hand synovitis and unilateral sacro-iliitis, was made. The correlation between DD, spondyloarthritis and psoriasis has been already anecdotally reported. Further observations may clarify if this association is more than casual.

Prospective capillaroscopy-based study on transition from primary to secondary Raynaud's phenomenon: preliminary results.

The objective of this prospective study was to investigate the transition from primary (PRP) to secondary (SRP) Raynaud's phenomenon (RP), in a large cohort of patients affected by isolated RP. A total of 2065 patients with RP were investigated by clinical interview, laboratory examinations, and nailfold videocapillaroscopy (NVC). Patients with negative NVC at first visit were yearly followed to monitor either the appearance of specific morphological alterations at NVC, or clinical manifestations of an underlying disease. Capillary abnormalities at NVC were scored, as well as the qualitative patterns of microangiopathy (Early, Active and Late). NVC was found negative at first visit in 1500 subjects; among them, 412 patients were evaluable and they were followed for a mean time of 5±4 years (range 2-13 years). Sixty-eight patients (16%) achieved a diagnosis of SRP during follow-up, showing normal or not specific capillary alterations at NVC 4% of patients (the diagnosis was undifferentiated connective tissue diseases), Early scleroderma-pattern 57%, Active scleroderma-pattern 7%, Late scleroderma-pattern 12%, and scleroderma-like pattern 18% of patients. The time of transition from normal/not specific capillary alterations to Early scleroderma-pattern was 4.4±3.8 years. Enlarged capillaries (diameter between 20 and 50 microns) and mild reduction of capillary density were found the more frequent markers at first NVC visit in patients who progressed to a scleroderma pattern (P=0.01). This study demonstrates in a large cohort, that almost 16% of patients initially diagnosed as affected by RP with negative NVC may transit to SRP during a mean follow-up of 4.4 years. PRP patients showing major notspecific alterations of nailfold capillaries at first NVC should be strictly monitored at least once a year since at higher risk of transition to SRP.

Has the clinical spectrum of gout changed over the last decades?

OBJECTIVES: To evaluate if the clinical spectrum of gout has changed over the last decades, a cohort of 107 patients was studied in relation to the date of disease onset and of presentation to our Institution. METHODS: The structured questionnaires of 107 consecutive patients with gout seen between 1989 and 2009 were retrospectively reviewed. Patients were divided into two subgroups according to the year of the first acute arthritis attack: (a) patients with gout onset dating back to 1967-2001, and (b) patients with gout of later (2002-2009) onset. The patients were also subdivided according to the date of their first admission to our Institution: 1989-2006 and 2007-2009 admissions. RESULTS: The male to female ratio changed from 11.3 in the patients who had the first attack before 2002 to 2.4 in the second onset group (p=0.02). A family history of gout was slightly more frequent in the second subgroup (22.7% vs. 6.4%, p=0.05). The mean number of acute attacks was higher in patients seen before 2002 (p=0.01). Synovial fluid was examined more frequently in the subgroup visited for the first time after 2006 (p=0.001). CONCLUSIONS: Our data indicating that the patients' sex ratio has changed over time, with women more frequently affected, could be of importance to clinicians who often believe that gout is a disease affecting males only. The increased utilisation of synovial fluid analysis suggests a closer attention to the disease in recent years. Clinicians should be aware that gout is increasingly affecting women.

Imaging of tophi with an extremity-dedicated MRI system.

OBJECTIVES: To describe the MRI features of gout tophi in the soft-tissues or joints of the limbs by low-field extremity-dedicated MRI. METHODS: Nine consecutive patients, 8M/1W, affected by chronic tophaceous gout were studied. Mean patients' age was 71.3±11.5 years, mean disease duration 98.1±44.9 months, and mean serum uric acid concentration 9.2±2.8 mg/L. Diagnosis was based on the ACR classification criteria for gout, and by identification of MSU crystals in the tophi and synovial fluid. Conventional radiograms and MRI with an extremity-dedicated system were obtained of the joint areas involved by tophi. RESULTS: At T1 weighted MRI images, all tophi showed a homogeneous intermediate signal intensity, similar to that of muscle. Conversely, in T2 weighted images, a wide spectrum of signal intensity patterns was observed. The pattern of contrast enhancement was variable from intense homogeneous to peripheral and heterogeneous. Capsulo-ligamentous structures were often thickened and degenerated and, on occasion, could be recognised as inhomogeneous, hypointense ribbon-shaped elements in the context of the tophus. In only two cases, tendons were infiltrated by tophaceous matter. Bone marrow oedema (BME) and erosions were seen in 8 out of 10 bones adjacent to tophi. CONCLUSIONS: The MRI appearance of gout tophi using an extremity-dedicated machine is similar to that described in the literature using whole body machines. BME adjacent to the tophus was a frequent finding. This technique may occasionally help in the differential diagnosis of nodules and in the follow-up of the disease. It also represents a useful tool to investigate the pathogenesis of gout and to better understand its clinical progression.

[The role of nailfold videocapillaroscopy in Raynaud's phenomenon monitoring and early diagnosis of systemic sclerosis]. / La videocapillaroscopia ungueale nel monitoraggio del fenomeno di Raynaud e nella diagnosi precoce della sclerosi sistemica.

Several connective tissue diseases, in particular systemic sclerosis (SSc), have Raynaud's phenomenon (RP) as their first clinical manifestation. Primary RP represents a benign condition often observed in otherwise healthy subjects, especially women: it is due to an exaggerated response to the physiological cold-induced vasospasm, whereas the secondary form of RP is typically associated with connective tissue diseases, especially SSc. Nailfold videocapillaroscopy (NVC), particulary after the recent technological advances, is a safe and reliable method to observe the microvascular structure and its early changes, especially during the transition from primary to secondary RP. In case of SSc, by considering validated patterns and scoring systems, NVC is the main tool that rheumatologists can rely on, besides the presence of specific auto-antibodies, to perform a very early diagnosis of the disease. This implies the possibility of early treatment of SSc, with an eye of predicting and preventing its major clinical complications.

Risk factors for gouty dactylitis.

OBJECTIVE: To investigate the risk factors associated with dactylitis in gout. METHODS: The questionnaires of 73 consecutive gouty patients, diagnosed according to the ACR criteria, were reviewed. They were consecutively screened for the presence of dactylitis. RESULTS: Seven out of 73 (9.6%) patients showed dactylitis. They had (1) longer disease duration, (2) a higher number of involved joints, (3) higher serum uric acid concentration, (4) more tophi, (5) higher ESR, and (6) a higher number of ACR criteria besides crystal identification, than the others. By logistic regression, renal stones (OR 13.3, 95% CI 1.1-158.3), upper extremity involvement (OR 4.9, 95% CI 1.4-16.6), number of ACR criteria (OR 1.9, 95% CI 1.1-3.3), and ESR (OR 1.02, 95% CI 1-1.04), significantly predicted dactylitis. CONCLUSIONS: Dactylitis is a feature of gout representing an indicator of disease severity.

[Clinical features of gout in a cohort of Italian patients]. / Caratteristiche cliniche della gotta in una coorte di pazienti Italiani.

OBJECTIVE: To assess the clinical characteristics of gout and its diagnostic approach in a group of Italian patients. METHODS: In a retrospective analysis, we evaluated 72 consecutive gouty patients examined in the years 2000-2007. We recorded demographic data, family history, comorbidities and disease characteristics (seasonality of the attacks, joints affected, serum uric acid concentration, and treatment). RESULT: 63/72 (87.5%) patients were men and 9 women, with mean age 61.9+/-13.7 years. 8/72 (11.1%) patients reported a familial history of gout. The first attack occurred mainly in the months of June, July and December. The first metatarsophalangeal joint was affected in 59.7% of patients and the hand in 25%. Treatment changed over the follow-up period, with a decreased use of NSAIDs (p<0.0001) and an increased use of colchicine (p=0.015) and allopurinol (p<0.0001). In 9 (12.5%) patients, joint aspiration was performed and monosodium urate crystals were found in synovial fluid or tophi. 42/72 (58.3%) patients fulfilled a minimum of 6 clinical criteria of the American College of Rheumatology, necessary for gout diagnosis. 47/72 (65.3%) patients, met the EULAR recommendations and had an 82% probability of being affected by gout. CONCLUSIONS: The diagnosis of gout is not always easy because of its changing clinical spectrum. Identification of MSU crystals in joint aspirates was obtained only in a minority of patients. In this setting the diagnosis with gout was often based on the observation of an acute intermittent monoarthritis involving mainly the first metatarsophlangeal joint, associated with hyperuricaemia and responsive to colchicine.

[Dynamic contrast-enhanced magnetic resonance imaging of the wrist in early arthritis]. / La risonanza magnetica dinamica del polso nella valutazione delle artriti precoci.

OBJECTIVES: MRI has been proposed as the imaging method of choice to evaluate the long-term outcome in patients with early arthritis. The role of dynamic MRI, performed at presentation, in predicting the outcome of patients with early arthritis has been addressed in the present study. METHODS: 39 patients with early arthritis, involving at least one wrist, were studied with clinical visits and laboratory investigations, every 3 months. Dynamic MRI was performed with a low-field (0.2T), extremity-dedicated machine (Artoscan, Esaote, Genova, Italy) equipped with a permanent magnet and with a dedicated hand and wrist coil. During the intravenous injection of Gd-DTPA, twenty consecutive fast images of 3 slices of the wrist were acquired. The synovial contrast enhancement ratio was calculated both as rate of early enhancement (REE) per second during the first 55" and as relative enhancement (RE) at t seconds. RESULTS: In our cohort of patients, REE and RE were significantly lower than those observed in a historical cohort of 36 patients with active rheumatoid arthritis. In univariate analysis, low RE predicted complete remission of arthritis. In multivariate analysis, fulfillment of RA criteria during follow-up was predicted by high RE. The need for immunosoppressive treatment at the end of follow-up was predicted by both low RE and high REE. CONCLUSIONS: Dynamic MRI may be used to predict several outcomes of early arthritis involving the wrist.

A computational continuum model of poroelastic beds.

Despite the ubiquity of fluid flows interacting with porous and elastic materials, we lack a validated non-empirical macroscale method for characterizing the flow over and through a poroelastic medium. We propose a computational tool to describe such configurations by deriving and validating a continuum model for the poroelastic bed and its interface with the above free fluid. We show that, using stress continuity condition and slip velocity condition at the interface, the effective model captures the effects of small changes in the microstructure anisotropy correctly and predicts the overall behaviour in a physically consistent and controllable manner. Moreover, we show that the performance of the effective model is accurate by validating with fully microscopic resolved simulations. The proposed computational tool can be used in investigations in a wide range of fields, including mechanical engineering, bio-engineering and geophysics.

[Immunoprophylaxis in the prevention of perinatal transmission of hepatitis virus B. Analysis of limiting factors]. / L'immunoprofilassi nella prevenzione della trasmissione perinatale del virus dell'epatite B. Analisi dei fattori limitanti.

The significance of obstetric anamnesis in neonatal risk identification and efficiency of a vaccinal schedule were investigated in order to verify the condition which limited the efficiency of immunoprophylaxis in the prevention of perinatal hepatitis B virus transmission. The data suggested that the lack of obstetric screening is the highest limitative factors in the realization of hepatitis B neonatal prevention. The immunoprophylaxis is surely a substantial method in the prevention of hepatitis B virus perinatal transmission, but the vaccinal schedule and follow-up should be improved.

Metabolic abnormalities in pain-processing regions of patients with fibromyalgia: a 3T MR spectroscopy study.

BACKGROUND AND PURPOSE: A growing body of evidence suggests the involvement of the brain in FM. The purpose of this proton MRS study was to test the hypothesis that there are metabolic alterations in some brain regions processing pain (VLPFC and thalamus) in patients with FM compared with HC. MATERIALS AND METHODS: Twelve patients with FM (30-54 years of age; mean age, 43.2 years), and 12 HC, matched for age and sex, underwent 1 session of single-voxel MRS performed on a 3T MR imaging scanner. MRS spectra were acquired with a PRESS for localization. The raw data from each spectrum was evaluated with an LCModel. T tests were used to evaluate differences of brain metabolites between groups. The Pearson correlation tested the relationship of metabolite ratios and clinical symptoms. RESULTS: Glx/Cr and Glu/Cr ratios within the VLPFC of both sides were significantly higher in patients than in HC (P < .01). No significant differences of metabolites between groups were found in the thalami. Positive correlations were found between Glu/Cr in the left thalamus and the VAS for pain (r = 0.730, P = .007) and between mIns/Cr in the right VLPFC and the VAS for pain (r = 0.607, P = .037) and the FIQ (r = 0.719, P = .008). CONCLUSIONS: The presence of elevated Glu/Cr levels in VLPFC strengthens the opinion that a complex neurophysiologic imbalance of different brain areas involved in pain processing underlies FM. These data may be useful in the diagnosis and development of more effective pharmacologic treatments.

Magnesium content of mononuclear blood cells in newborn infants and its correlation with maternal magnesium status.

In 25 full-term infants at birth and in their mothers, we determined plasma and mononuclear blood cell (MBC) Mg levels in order to investigate the relationship between maternal and fetal Mg status. MBC isolation for Mg analysis was carried out with a Ficoll-Isopaque gradient which is commercially available in disposable tubes. There was no difference in the plasma and MBC Mg levels between infants and their mothers. Neonatal MBC Mg content was significantly correlated with maternal plasma Mg concentration. The data demonstrate that MBC Mg content does not present any difference on the basis of age and emphasize that the constitution of fetal Mg reserve depends on maternal plasma Mg concentration.