Chronic E. Coli Drug-Resistant Cystitis Treated with a Sequence of Modulated Extremely Low-Frequency Electromagnetic Fields: A Randomized Study of 148 Cases.

(1) Background: This study investigated the effects of sequenced electromagnetic fields, modulated at extremely low frequencies and intensities, in the treatment of drug-resistant Escherichia coli (E. coli)-induced chronic bacterial cystitis. (2) Methods: A total of 148 female participants, aged 18 to 80 years diagnosed with chronic bacterial cystitis caused by drug-resistant E. coli, were recruited for this study. Participants were randomly assigned to two groups: an experimental group (n = 74) with osteopathic palpation and assessment treated with a sequence of electromagnetic fields, and a control group (n = 74) receiving a placebo treatment. Both groups were assessed at this study's outset, 4 weeks after eight applications, and at 12 weeks for symptomatic presentation and laboratory parameters. (3) Results: After 4 weeks of treatment, a significant difference was observed between the two groups regarding D-DIMER levels, IL-6 levels, erythrocyte levels, leukocyte levels, and E. coli levels (p < 0.001). By the 12th week, the experimental group continued to exhibit a significant reduction in the examined parameters compared to the control group (p < 0.001). Additionally, the treatment did not induce any side effects in the patients in the experimental group. (4) Conclusions: Treatment with coherently sequenced electromagnetic fields, modulated at an extremely low frequency and intensity, not only appears to provide an effective alternative for the symptoms of chronic bacterial cystitis caused by drug-resistant E. coli but also demonstrates a potent antibacterial effect.

Role of Jagged1-Notch pathway in thyroid development.

The zebrafish thyroid gland shows a unique pattern of growth. Despite the lack of a compact gland, the zebrafish thyroid tissue originates from the pharyngeal endoderm and the main genes involved in its patterning and early development are conserved between zebrafish and mammals. In recent years, the research has been focused to the search of novel candidate genes and environmental factors underlying congenital hypothyroidism. Among these, it has been demonstrated that the Notch signalling plays a central role during zebrafish thyroid development. In this review, we will provide an overview of the current knowledge of the distinct roles of the Notch signalling and of the jag1a and jag1b ligands during the different phases of thyroid organogenesis. Furthermore, we will discuss the role of JAG1 variants in congenital thyroid defects.

Manual evaluation of the diaphragm muscle.

The respiratory diaphragm is the most important muscle for breathing. It contributes to various processes such as expectoration, vomiting, swallowing, urination, and defecation. It facilitates the venous and lymphatic return and helps viscera located above and below the diaphragm to work properly. Its activity is fundamental in the maintenance of posture and body position changes. It can affect the pain perception and emotional state. Many authors reported on diaphragmatic training by using special instruments, whereas only a few studies focused on manual therapy approaches. To the knowledge of the authors, the existing scientific literature does not exhaustively examines the manual evaluation of the diaphragm in its different portions. A complete evaluation of the diaphragm is mandatory for several professional subjects, such as physiotherapists, osteopaths, and chiropractors not only to elaborate a treatment strategy but also to obtain information on the validity of the training performed on the patient. This article aims to describe a strategy of manual evaluation of the diaphragm, with particular attention to anatomical fundamentals, in order to stimulate further research on this less explored field.

The fascial system and exercise intolerance in patients with chronic heart failure: hypothesis of osteopathic treatment.

Chronic heart failure is a progressive, debilitating disease, resulting in a decline in the quality of life of the patient and incurring very high social economic costs. Chronic heart failure is defined as the inability of the heart to meet the demands of oxygen from the peripheral area. It is a multi-aspect complex disease which impacts negatively on all of the body systems. Presently, there are no texts in the modern literature that associate the symptoms of exercise intolerance of the patient with a dysfunction of the fascial system. In the first part of this article, we will discuss the significance of the disease, its causes, and epidemiology. The second part will explain the pathological adaptations of the myofascial system. The last section will outline a possible osteopathic treatment for patients with heart failure in order to encourage research and improve the general curative approach for the patient.

Increased risk for non-autoimmune hypothyroidism in young patients with congenital heart defects.

CONTEXT: Newborns with congenital hypothyroidism (CH) have an increased risk for congenital heart defects (CHD) due to a common embryonic developmental program between thyroid gland and heart and great vessels. OBJECTIVE: Our objective was to investigate the prevalence and origin of thyroid disorders in young patients with CHD. DESIGN AND SETTING: We conducted a prospective observational study between January 2007 and January 2009 in academic Pediatric Cardiosurgery and Endocrinology. PATIENTS: Patients included 324 children (164 males, 160 females, aged 0.2-15.4 yrs) with CHD. INTERVENTION: Subjects underwent hormonal and genetic screening. MAIN OUTCOME MEASURES: Serum TSH and thyroid hormone levels were assessed. RESULTS: Two CHD patients were diagnosed with CH at the neonatal screening (1:162). Mild hypothyroidism (serum TSH > 4.0 µU/ml) was diagnosed and confirmed 6 months later [TSH = 5.4 ± 1.5 µU/ml; free T(4) = 1.3 ± 0.2 ng/dl (normal values 0.8-1.9)] in 37 children (11.5%) who were negative at neonatal screening. Hypothyroidism was not related to type of CHD, whereas TSH levels positively correlated with serum N-terminal pro-type B natriuretic peptide levels. Biochemical and ultrasound findings consistent with thyroid autoimmunity were present in three of 37 hypothyroid children (8.1%). One patient had hemiagenesis (2.7%). Variations in candidate genes were screened in CHD patients. NKX2.5 coding sequence was normal in all samples. A 3-Mb microdeletion in 22q11.2 was detected in three patients (8.3%), whereas only known polymorphisms were identified in TBX1 coding sequence. CONCLUSIONS: CHD patients have an increased risk for both CH (10-fold higher) and acquired mild hypothyroidism (3-fold higher). Unrecognized mild hypothyroidism may negatively affect the outcome of CHD children, suggesting that thyroid function should be repeatedly checked. Thyroid autoimmunity and 22q11.2 microdeletions account for small percentages of these cases, and still unknown mechanisms underline such a strong association.

Syndromes of resistance to TSH.

The resistance to TSH action is a genetic disease characterized by molecular defects hampering the adequate transmission of TSH stimulatory signal into thyroid cells. In principle the defect may affect every step along the cascade of events following the binding of TSH to its receptor (TSHR) on thyroid cell membranes. The phenotypic expressivity of TSH resistance is highly variable going from severe congenital hypothyroidism (CH) with thyroid hypoplasia to mild hyperthyrotropinemia (hyperTSH) associated with an apparent euthyroid state. More severe forms follow a recessive pattern of inheritance and occur in patients with biallelic mutations both causing a severe loss of TSHR function. Differential diagnosis in these cases includes the exclusions of other causes of isolated thyroid dysgenesis. Mildest forms may instead occur in patients with monoallelic TSHR defects following a dominant mode of inheritance. In these cases we described the dominant negative effect exerted by some mutants on the activity of the receptor encoded by the wild type allele. In these cases, differential diagnosis involves the exclusion of autoimmune thyroid disease or pseudohypoparathyroidism associated with defects at the GNAS locus. This review will focus on the variable clinical expression of this disease.

Biased TCR gene usage in alloreactive T cells specific for a structurally dissimilar MHC alloantigen.

Two models of allorecognition of MHC molecules have been proposed. One emphasizes specificity for MHC molecule-bound peptides and the other for exposed MHC polymorphisms. We predicted that the latter model would predominate in responder:stimulator combinations whose MHC molecules differed extensively in their TCR-contacting surfaces and that this would be reflected in biased TCR usage. Two panels of anti-DR11 T cell clones were generated, one from a DR17 and the other from a DR15 responder. The TCR-contacting surfaces of DR17 and DR11 have multiple differences, and those of DR15 and DR11 are very similar. TCR analysis by polymerase chain reaction amplification and mAb staining revealed that five out of nine DR17 anti-DR11 clones used the V beta 13 and two the V beta 6, family. In contrast seven different V beta families were used by the eight DR15 anti-DR11 clones. A similar bias in TCR V beta usage was observed in the polyclonal DR17 and DR11 T cell lines from which the clones were derived, and in a second DR17 anti-DR11 line from a different individual. These results support the concept that specificity for the foreign MHC structure itself may play an important role in the alloresponse between responders and stimulators with structurally dissimilar MHC molecules.

Hepatitis C virus testing in primary biliary cirrhosis.

We retrospectively investigated anti-HCV prevalence in a series of 160 consecutive patients with primary biliary cirrhosis who presented between 1980 and 1989. Of these, 19 (12%) were positive for anti-HCV by C-100 ELISA. Serum IgG levels were significantly higher in anti-HCV-positive patients and correlated to optical density values. A serum sample was again collected from all the patients from the same series who were seen in 1990 for follow-up, after a median period of 32 months. Anti-HCV positivity was found to be substantially unchanged in this subgroup of patients when the freshly drawn blood samples were retested with C-100 ELISA, while it increased from 10% to 17% when second generation ELISA was used. Three of the C-100 ELISA positive samples were C-100 RIBA reactive, and six of the second generation ELISA positive samples were 4-RIBA reactive. The HCV genome was not detected in any of the seven anti-HCV C-100 ELISA and second generation ELISA positive sera which were studied by polymerase chain reaction, including four cases confirmed by 4-RIBA. Life expectancy, as determined by survival analysis, did not differ significantly between anti-HCV-positive and -negative patients. These findings suggest that anti-HCV positivity does not influence the clinical presentation and course of primary biliary cirrhosis.

Antibodies to hepatitis C virus in primary biliary cirrhosis.

We investigated the prevalence of anti-HCV in 160 consecutive patients with primary biliary cirrhosis. By ELISA, 19 (12%) were positive, as compared to a 68% prevalence in 135 patients with chronic non-A, non-B hepatitis. Serum IgG levels were significantly higher in the anti-HCV positive group. By RIBA, seropositivity was confirmed for 4 patients, whereas 7 were indeterminate. A slight, non-significant reduction of life expectancy was found in anti-HCV positive patients. Until reliable and independent confirmatory tests become available, definitive conclusions on the importance of anti-HCV positivity in primary biliary cirrhosis are improper.

CD1+ thymocytes proliferate and give rise to functional cells after stimulation with monoclonal antibodies recognizing CD3, CD2 or CD28 surface molecules.

The signal requirements for activation and proliferation of CD1+ thymocytes have been studied in order to define whether this immature cell population could function as mature T cells do. We found that CD1+ cells expressed high levels of CD25 antigen upon triggering with specific monoclonal antibodies (mAbs) (anti-CD3, anti-CD2, anti-CD28) in association with low doses of Phorbol-13-myristate-12-acetate (PMA). More interestingly, we described that in the presence of PMA CD1+ thymocytes proliferate upon stimulation with anti-CD28 mAb as well as with a pair of anti-CD2 mAbs, without the need of exogenous interleukin-2 (IL2), whereas they respond to anti-CD3 mAb only if exogenous IL2 was provided. Furthermore, CD1+ cells stimulated under optimal proliferative conditions, gave rise to cell populations capable of lysing natural killer (NK)-sensitive (K562) and NK-resistant (MEL 10, Daudi, EPA1) tumor target cells. These data strongly support the idea that CD1+ thymocytes, under appropriate stimulations, display some of the functional capabilities of mature T cells.

[Factor VII and cardiovascular risk in obese subjects]. / Fattore VII e rischio cardiovascolare negli obesi.

We investigated whether or not obesity is related to increased factor VII activity. We studied 70 obese subjects (aged 25 to 50 years, 25 males and 45 females, body mass index (BMI): mean +/- SD = 32.44 +/- 5.44) and 33 non-obese subjects (aged 25 to 50 years, 12 males and 21 females, BMI: mean +/- SD = 21.80 +/- 1.70). None of them were smokers or affected by hyperlipidemia, diabetes mellitus, impaired glucose tolerance or arterial hypertension. Factor VII activity was measured by the coagulometric method. We found higher factor VII activity in obese subjects (115.74 +/- 26.10%) than in healthy subjects (98.55 +/- 23.49%, p less than 0.005). Increased factor VII levels could determine a thrombophilic state involved in the genesis of cardiovascular accidents in obesity.

Simultaneous cytofluorometric analysis for the expression of cytoplasmic antigens and DNA content in CD3- human thymocytes.

We describe a method of two-color immunofluorescence staining which allows the simultaneous analysis of both cytoplasmic antigens and cell entry into the S/G2/M cell cycle phases. This analysis was performed on CD3(-)-activated thymocytes obtained from either highly purified CD1-CD3-CD4-CD8- cells or fresh thymus cell suspensions, stimulated with low doses of phorbol-12 myristate-13 acetate (0.5 ng/ml) and interleukin-2. On the 14th day under these culture conditions about 90% of thymocytes did not express CD3 antigen on the cell surface. CD3- cells were further purified by cell sorting, fixed in paraformaldehyde, and permeabilized with Nonidet-P40. Then these thymocytes were stained by indirect immunofluorescence with monoclonal antibodies identifying T cell-specific molecules (CD3, CD2, CD28, TCR alpha/beta, and TCR gamma/delta) and analyzed for DNA content. Interestingly, both CD3 and CD28 antigens were detectable in the cytoplasm of most cells (greater than 80%). Further, the majority of the thymocytes which had entered the S/G2/M phases of the cell cycle (20%) expressed intracellular CD3 and CD28 molecules and reacted with the anti-beta framework beta F1 monoclonal antibody. The relationship between the appearance of CD3 and other T cell markers in the cytoplasm, the cell cycle entry, and the thymocyte development is discussed.