Observations about subcalcaneal adventitial bursitis (heel fat pad inflammatory lesion) in rheumatoid arthritis. Comment on the article of Suzuki and Shirai.

Not available.

Expanding the clinical and genetic spectra of NKX6-2-related disorder.

Hypomyelinating leukodystrophies (HLDs) affect the white matter of the central nervous system and manifest as neurological disorders. They are genetically heterogeneous. Very recently, biallelic variants in NKX6-2 have been suggested to cause a novel form of autosomal recessive HLD. Using whole-exome or whole-genome sequencing, we identified the previously reported c.196delC and c.487C>G variants in NKX6-2 in 3 and 2 unrelated index cases, respectively; the novel c.608G>A variant was identified in a sixth patient. All variants were homozygous in affected family members only. Our patients share a primary diagnosis of psychomotor delay, and they show spastic quadriparesis, nystagmus and hypotonia. Seizures and dysmorphic features (observed in 2 families each) represent an addition to the phenotype, while developmental regression (observed in 3 families) appears to be a notable and previously underestimated clinical feature. Our findings extend the clinical and mutational spectra associated with this novel form of HLD. Comparative analysis of our 10 patients and the 15 reported previously did, however, not reveal clear evidence for a genotype-phenotype correlation.

Transcatheter closure of PFO as secondary prevention of cryptogenic stroke.

This article covers the main unsolved issues regarding the potential role that the patent foramen ovale (PFO) plays in the genesis of so-called cryptogenic stroke. Some brief notions of the anatomy and epidemiology of the PFO are outlined. Subsequently, the results of the three trials on secondary prevention (medical therapy vs. transcatheter closure) in patients with PFO and a history of cryptogenic stroke are presented. The conflicting results of numerous meta-analyses derived from the three randomized controlled trials are discussed. Official scientific guidelines dispute an alleged superior efficacy of transcatheter PFO occlusion in comparison with antithrombotic therapy alone (anticoagulants or antiplatelet agents), except for selected cases of patients with documented PFO and a concomitant clinical-instrumental picture of deep venous thrombosis. Nevertheless, considering recent doubts about the presumptive thrombogenic and arrhythmogenic potential of PFO occlusion, which concerns only one of the septal occluders previously used, further in-depth investigations are warranted, centered on the use of newer dedicated devices to be tested in comparison with antithrombotic regimens alone.

Platypnea-orthodeoxia syndrome : Orthostatic dyspnea and possible pathophysiological substrates.

Platypnea-orthodeoxia syndrome (POS) is a rare disorder characterized by the emergence of a right-to-left shunt at the intracardiac or intrapulmonary level. The clinical picture is distinguished by shortness of breath that worsens on standing due to an accentuation of oxygen desaturation, and instead improves, at least partly, in the recumbent position. In this article we present a brief review of the pathophysiology of POS, as well as its clinical picture, diagnostic assessment, and preferential therapeutic options. Pathophysiological issues that are still not completely understood or much debated are outlined. The currently accepted pathophysiological concepts are presented and a summary of the main diagnostic and therapeutic tools is provided.

Effects of limiting fluid intake on clinical and laboratory outcomes in patients with heart failure. Results of a meta-analysis of randomized controlled trials.

BACKGROUND: The guidelines of the Scientific Societies of Cardiology recommend limiting fluid intake as a nonpharmacological measure for the management of chronic heart failure (HF). However, many patients with HF may suffer from severe thirst. A meta-analysis was performed to evaluate the effect of limiting fluid consumption based on various clinical and laboratory outcomes in patients with chronic HF. METHODS: Only randomized controlled trials comparing liberal and restricted fluid oral intake in patients with HF were included. Primary outcomes were HF hospitalizations and all-cause mortality. Secondary outcomes were the sensation of thirst, the duration of therapy with intravenous diuretics, and the serum levels of creatinine, sodium, and B-type natriuretic peptide (BNP). RESULTS: Six studies met the inclusion criteria. Significant heterogeneity was detected for the majority of outcomes. In 5 studies, patients with restricted fluid intake compared to patients with free consumption of beverages had similar rehospitalization and mortality rates. There were no differences regarding patients' sense of thirst (4 studies), duration of intravenous diuretic treatment (2 studies), serum creatinine levels (5 studies), and serum sodium levels (5 studies). Serum BNP levels were significantly higher in the group with free fluid intake (4 studies). CONCLUSION: In patients with HF, liberal fluid consumption does not seem to exert an unfavorable impact on HF rehospitalizations or all-cause mortality. Further randomized controlled trials are warranted to definitively confirm the present findings.

Complications of unintentional dural puncture during labour epidural analgesia: a 10-year retrospective observational study.

INTRODUCTION: Unintentional dural puncture (UDP) occurs in 0.5-1.5% of labour epidural analgesia cases. To date, little is known about evidence of UDP-related complications. This work aimed to assess the incidence of intrapartum and postpartum complications in parturients who experienced UDP. METHODS: This is a 10-year retrospective observational study on parturients admitted to our centre who presented UDP. Data collection gathered UDP-related complications during labour and postpartum. All women who displayed UDP received medical therapy and bed rest. An epidural blood patch (EBP) was not used in this population. Once asymptomatic, patients were discharged from the hospital. RESULTS: Out of 7718 neuraxial analgesia cases, 97 cases of UDP occurred (1.25%). During labour, complications appeared in a small percentage of analgesia procedures performed, including total spinal anaesthesia (1.0%), extended motor block (3%), hypotension (4.1%), abnormal foetal heart rate (2%), inadequate analgesia (14.4%), and general anaesthesia following neuraxial anaesthesia failure (33.3% of emergency caesarean sections). During the postpartum period, 53.6% of parturients exhibited a postdural puncture headache, 13.4% showed neurological symptoms, and 14.4% required neurological consultation and neuroimaging. No patient developed subdural hematoma or cerebral venous sinus thrombosis; one woman presented posterior reversible encephalopathy syndrome associated with eclampsia. Overall, 82.5% of women experienced an extension of hospital stay. CONCLUSION: Major complications occurred in a small percentage of patients during labour. However, since they represent high-risk maternal and neonatal health events, a dedicated anaesthesiologist and a trained obstetric team are essential. No major neurological complications were registered postpartum, and EBP was not performed. Nevertheless, all patients with UDP were carefully monitored and treated until complete recovery before discharge, leading to an extension of their hospitalization.

Obstructive sleep apnea: neurocognitive and behavioral functions before and after treatment.

Obstructive sleep apnea syndrome (OSAS) is a sleep disorder characterized by repetitive episodes of upper airway obstruction. The aim of this study was to evaluate whether continuous positive airway pressure (CPAP) treatment is linked to improvements in cognitive abilities and emotional functions of patients with OSAS. Following the exclusion of four subjects for non-adherence to CPAP treatment, the final study sample was composed of 16 patients with moderate-to-severe OSAS, who were assessed both prior to and after 3 months of CPAP treatment, using a neuropsychological battery and questionnaires to assess mood and anxiety disorders, irritability, quality of life, quality of sleep and daytime sleepiness. We observed significant improvements in Digit Span Backward, Short Story and Corsi Span performances after 3 months of CPAP treatment. Questionnaires showed a significant reduction in daytime sleepiness and improvements in the subjective perception of sleep quality and sleep efficiency, and reduced daytime dysfunction. CPAP treatment has significant effects on different cognitive domains in patients with OSAS, especially working memory, long-term verbal memory, and short-term visuospatial memory.

Improvement of clinical response in allergic rhinitis patients treated with an oral immunostimulating bacterial lysate: in vivo immunological effects.

Allergic rhinitis is known to be one of the most common chronic diseases in the industrialized world. According to the concept that allergic rhinitis patients generally suffer from an immune deficit, in order to stimulate specifically or aspecifically their immune system, immunomodulating agents from various sources, such as synthetic compounds, tissue extracts or a mixture of bacterial extracts, have been used. The aim of the present trial is to evaluate the efficacy of the treatment with an immunostimulating vaccine consisting of a polyvalent mechanical bacterial lysate (PMBL) in the prophylaxis of allergic rhinitis and subsequently to analyze its in vivo effects on immune responses. 41 allergic rhinitis patients were enrolled: 26 patients were randomly assigned to the group for PMBL sublingual treatment and 15 others to the group for placebo treatment. For all 26 patients blood samples were drawn just before (T0) and after 3 months of PMBL treatment (T3) to evaluate plasma IgE levels (total and allergen-specific) and the cytokine production involved in the allergic response (IL-4, IFN-gamma). The results of our study indicate that PMBL is effective in vivo in the reduction or in the elimination of the symptoms in rhinitis subjects during the treatment period in comparison to a non-immunostimulating treatment. A significant and clinically relevant improvement was found in 61.5%, a stationary clinical response was registered in 38.4% and no negative side effects associated with the medication or worsening were recorded. At the end of a 3-month follow up period the clinical picture remained the same as that observed at T3. PMBL treatment did not affect the serum IgE levels (either total or allergen-specific) and did not induce significant changes in IFN-gamma concentration. In contrast, PMBL therapy may be accompanied, in some patients, by a potential immunomodulating activity by decreasing IL-4 cytokine expression.

Prolonged complete hematologic response in relapsed/refractory T-large granular lymphocyte leukemia after bendamustine treatment.

T-large granular lymphocyte leukemia (T-LGLL) is a chronic clonal proliferation of effector memory cytotoxic CD3+CD57+CD56- T cells and the current guidelines suggest immunosuppressive therapy as first-line therapy, but the treatment of refractory/relapsed patients is still challenging due to the lack of prospective studies. We describe a series of two refractory/relapsed T-LGLL patients successfully treated with bendamustine, a chemotherapeutic agent largely used for B-cell neoplasms, but poorly investigated for the treatment of T-cell diseases. Complete remission (CR) was achieved in 3 and 6 months, respectively, and maintained for at least 20 months. One patient relapsed after a 20-month CR, but she was responsive to bendamustine therapy again, obtaining a further prolonged CR. Bendamustine as single agent or in combination could be a feasible therapeutic option in refractory/relapsed T-LGLL, especially for elderly patients because of its safety profile.

Environmental factors associated with Bartonella vinsonii subsp. berkhoffii seropositivity in free-ranging coyotes from northern California.

Bartonella vinsonii subsp. berkhoffii is a newly recognized pathogen of domestic dogs and humans. Coyotes (Canis latrans) are considered an important reservoir of this bacterium in the western United States, but its vectors are still unknown. Our objective was to identify environmental factors associated with Bartonella antibody prevalence in 239 coyotes from northern California, using an enzyme-linked immunosorbent assay. In addition, associations were evaluated between B. v. berkhoffii and two pathogens with known vectors and habitat requirements, Dirofilaria immitis and Anaplasma phagocytophilum. Overall, B. v. berkhoffii seroprevalence was 28% (95% confidence interval [CI], 22.3%, 33.7%) and Bartonella seropositive coyotes were more likely than seronegative coyotes to be positive for Anaplasma phagocytophilum (Odds ratio = 3.3; 95% CI = 1.8, 5.9) and Dirofilaria immitis (Odds ratio = 2.1; 95% CI = 1.2, 3.8). The most likely geographic clusters of Bartonella and Dirofilaria overlapped. Bartonella seropositivity was associated with higher precipitation (p = 0.003) and proximity to the coast (p = 0.007) in univariate analysis. The association with precipitation varied with season, based on a logistic regression model.

Glutathione S-conjugates stimulate ATP hydrolysis in the plasma membrane fraction of rat hepatocytes.

Incubation of a rat hepatocyte plasma membrane fraction with micromolar concentrations of either glutathione disulfide or various glutathione S-conjugates resulted in a several-fold increase in the rate of ATP hydrolysis. This stimulation was further enhanced when the plasma membrane fraction had been pretreated with agents that arylate or oxidize sulfhydryl groups, suggesting that this ATPase activity is modulated by the protein thiol status of the plasma membrane. It is proposed that this newly discovered ATPase may function in the cellular extrusion of both glutathione disulfide and glutathione S-conjugates.

Evidence that TRPC3 is a molecular component of the 1alpha,25(OH)2D3-activated capacitative calcium entry (CCE) in muscle and osteoblast cells.

In chick skeletal muscle and in rat osteoblast-like cells (ROS 17/2.8), 1alpha,25-dihydroxy-Vitamin-D(3) [1alpha,25(OH)(2)D(3)] stimulates release of Ca(2+) from inner stores and extracellular cation influx through both voltage-dependent and capacitative Ca(2+) entry (CCE) channels. We investigated the involvement of TRPC proteins in CCE induced by 1alpha,25(OH)(2)D(3). Two fragments were amplified by RT-PCR, exhibiting >85% sequence homology with human TRPC3. Northern and Western blots employing TRPC3-probes and anti-TRPC3 antibodies, respectively, confirmed endogenous expression of a TRPC3-like protein. Both cell types transfected with anti-TRPC3 antisense oligodeoxynucleotides showed reduced CCE and Mn(2+) entry induced by either thapsigargin or 1alpha,25(OH)(2)D(3). In muscle cells, anti-VDR antisense inhibited steroid-induced Ca(2+) and Mn(2+) influx and co-immunoprecipitation of TRPC3 and VDR was observed, suggesting an association between both proteins and a functional role of the receptor in 1alpha,25(OH)(2)D(3) activation of CCE. In osteoblasts, two PCR fragments showing high homology with human INAD-like sequences were obtained. Northern blot and antisense functional assays suggested the involvement of the INAD-like protein in CCE regulation by the hormone. Therefore, we propose that an endogenous TRPC3 protein mediates 1alpha,25(OH)(2)D(3) modulation of CCE in muscle and osteoblastic cells, which seems to implicate VDR-TRPC3 association and the participation of a INAD-like scaffold protein.

Isolated atrial inversion in situs inversus: a rare anatomic arrangement.

Isolated atrial inversion in situs inversus is a rare congenital cardiac malformation. Its physiology resembles transposition of great vessels, and the best option for its surgical treatment is the atrial switch operation. In this article, we present a case of isolated atrial inversion in concordance with visceral situs inversus diagnosed at birth by echocardiography and cardiac catheterization, which was successfully treated at 8 months of age by a Senning procedure.

Optimizing efficacy of quick parathyroid hormone determination in the operating theater.

The usefulness of intraoperative parathyroid hormone (PTH) monitoring has been extensively documented in primary hyperparathyroidism (HPT), whereas few data have been published on its use in reoperations or in secondary and tertiary HPT. We report our initial experience with a rapid (12 min response) PTH immunochemiluminometric assay performed in the operating room during surgery in 12 patients with primary HPT, 16 end-stage renal disease patients with secondary HPT and five kidney transplanted subjects with tertiary HPT. Blood samples were taken at baseline, within 10 min after resection and subsequently at various intervals whenever needed. The mean PTH levels before and after parathyroidectomy were 230.5 pg/mL (range 69-842) and 47.3 pg/mL (range 5-184), respectively, in primary HPT, 855.0 pg/mL (416-1655) and 202.2 pg/mL (53-440) in secondary HPT, and 205.6 pg/mL (116-301) and 45.4 pg/mL (18-97) in tertiary HPT. All patients but one had a significant percentage decline from pre-excision values (mean 76.9%, 76.0%, and 76.1% in primary, secondary and tertiary HPT, respectively). While a reduction of more than 50% was observed in 30 out of 33 patients after the first intraoperative sampling, additional measurements were performed in 10 cases. On-site PTH monitoring with this user-friendly and reliable system has proved helpful in targeting PTH tests to give the surgeon a rapid and accurate assessment of the intervention. The development of optimal PTH sequence strategies with decision-focused analytical and clinical limits will improve the efficacy of "point-of-care" PTH assay and resource utilization.

Effects of silver in isolated rat hepatocytes.

Addition of silver nitrate or silver lactate to freshly isolated hepatocytes caused dose-dependent loss of cell viability, measured by trypan blue exclusion, at concentrations within 30-70 microM. Silver cytotoxicity was accompanied by a decrease in hepatic thiol concentration and an increase in lipid peroxidation. Treatment of hepatocytes with the reduced glutathione (GSH)-depleting agent diethylmaleate markedly increased their vulnerability to silver toxicity whereas protective effects were produced by the thiol-reducing agent, dithiothreitol. Both alpha-tocopherol, which protected from the onset of silver-associated lipid peroxidation, and the iron chelator agent, deferoxamine failed to prevent loss of cell viability. These data suggest that perturbation of intracellular thiol homeostasis may play a critical role in the mechanism underlying silver-induced lethal damage to isolated rat hepatocytes.

Coronally advanced flap procedure for root coverage. Is flap thickness a relevant predictor to achieve root coverage? A 19-case series.

This clinical study was designed to determine whether the thickness of the flap can influence root coverage when gingival recessions associated with traumatic toothbrushing are treated using a coronally advanced flap (CAF). Nineteen patients, aged from 25 to 57 years, with high levels of oral hygiene (full-mouth plaque scores <20%) were selected for the study. Each patient contributed with one Miller Class I or II maxillary or mandibular recession. A total of 19 recessions > or =2 mm were treated. After local anesthesia and before flap elevation, the exposed root surface was planed with a sharp curet. A trapezoidal full- and partial-thickness flap was then elevated, displaced coronally, and sutured to cover the treated root surface. Before suturing, flap thickness was measured in the alveolar mucosa with a gauge. After surgery, all patients were recalled for control and professional prophylaxis once a week during the first month and monthly up to the third month. The mean initial recession depth was 3.0+/-0.9 mm. Mean flap thickness (FT) was 0.7+/-0.2 mm. Three months later, mean recession depth was 0.6+/-0.6 (P <0.0001) and mean recession reduction was 2.4+/-0.7 mm. Mean root coverage was 82+/-17%. Flap thickness >0.8 mm was associated with 100% of root coverage. The results of this study indicate that there is a direct relation between flap thickness and recession reduction (P <0.0001).

Coronally advanced flap procedure for root coverage. Treatment of root surface: root planning versus polishing.

This clinical study was designed to determine if mechanical instrumentation (root planing) of the exposed root is useful in treating gingival recession caused by traumatic toothbrushing following a coronally advanced flap (CAF). Ten patients with high levels of oral hygiene (full-mouth plaque score <20%), from 25 to 57 years of age, were selected for the study. Each patient showed 2 bilateral Class I or II maxillary recessions. A total of 20 recessions were treated. The difference in the recessions was < or =1 mm. In each patient, one recession was randomly assigned to the test group and the contralateral one to the control group. In the test group, the exposed root surface was polished at slow speed with a rubber cup and prophylaxis paste for 60 seconds. In the control group, the exposed root surface was planed with a sharp curet. In both test and control groups, a trapezoidal full- and partial-thickness flap was elevated, coronally displaced, and sutured to cover the treated root surface. Before treatment, the mean recession depth in the test group (polishing) was 3.1+/-1.1 mm; and in the control group (root planing), 2.9+/-1.0 mm. Three months after the described procedures, the test group (polishing) showed a mean recession reduction of 2.6+/-0.6 mm; mean percent root coverage was 89+/-14%. In the control group (root planing), the mean recession reduction was 2.3+/-0.7 mm and mean percent root coverage was 83+/-16%. The difference of recession reduction between the test and control group was not statistically significant (P = 0.1405), even though the test group showed slightly better clinical results in terms of root coverage. This prospective clinical, controlled, randomized study shows that mechanical instrumentation (root planing) of the exposed root surfaces is not necessary when shallow recessions caused by traumatic toothbrushing are treated using a coronally advanced flap (CAF) in patients with high levels of oral hygiene.

Coronally advanced flap procedure: is the interdental papilla a prognostic factor for root coverage?

BACKGROUND: This study was designed to verify if the dimension of the interdental papilla may be a prognostic factor for the clinical outcome of the coronally advanced flap (CAF) in the treatment of gingival recessions. METHODS: Thirty-three Miller Class I recessions were treated in 33 patients using the CAF procedure. Two types of measurements were performed: 1) clinical measurements (probing depth, recession depth, width of keratinized tissue, clinical attachment level) were recorded at baseline and 3 months after surgery and 2) all recessions were photographed and transformed into computer images. A specific software allowed recording of both linear and square measurements. The following digital measurements were recorded at baseline: 1) base, height, and area of the mesial and distal papillae adjacent to the involved tooth and 2) width/depth of the recession and the area of the exposed root surface of the involved tooth. The residual recession area, if any, was recorded 3 months after surgery. The digital measurements of the height and of the area of the papilla were used in statistical analysis (multiple linear regression and logistic regression) to evaluate a possible correlation with root coverage (mm2) and/or with complete root coverage. RESULTS: Root coverage was not significantly correlated to the papilla area (P= 0.3692) or to papilla height (P= 0.0968). The complete root coverage was not correlated to the papilla area (P= 0.3181), but it was correlated to papilla height (P= 0.0499). CONCLUSIONS: This study indicates that the root coverage following CAF procedure is not significantly correlated to papilla dimension. However, complete root coverage is significantly more frequent in sites with lower height of the adjacent papilla.