Effects of Gender and Vitamin D on Vascular Reactivity of the Carotid Artery on a Testosterone-Induced PCOS Model.

The negative cardiovascular effects of polycystic ovary syndrome (PCOS) and vitamin D deficiency (VDD) have been discussed previously; however, the sex differences between PCOS females and males are not yet known. Our aim was to investigate the effect of PCOS and VDD in the carotid artery of male and female Wistar rats. Females were treated with transdermal testosterone (Androgel) for 8 weeks, which caused PCOS. VDD and vitamin D supplementation were accomplished via diet. The carotid arteries' contraction and relaxation were examined using myography. Receptor density was investigated using immunohistochemistry. In PCOS females, angiotensin receptor density, angiotensin II-induced contraction, androgen receptor optical density, and testosterone-induced relaxation increased. The increased contractile response may increase cardiovascular vulnerability in women with PCOS. As an effect of VDD, estrogen receptor density increased in all our groups, which probably compensated for the reduced relaxation caused by VDD. Testosterone-induced relaxation was decreased as a result of VDD in males and non-PCOS females, whereas this reduction was absent in PCOS females. Male sex is associated with increased contraction ability compared with non-PCOS and PCOS females. VDD and Androgel treatment show significant gender differences in their effects on carotid artery reactivity. Both VDD and PCOS result in a dysfunctional vascular response, which can contribute to cardiovascular diseases.

How to evaluate over 60 million blood glucose data - The design of the MÉRY Diabetes Database.

AIMS: The aim of the article is to describe the method for creating a close to ideal diabetes database. The MÉRY Diabetes Database (MDD) consists of a large quantity of reliable, well-maintained, precise and up-to-date data suited for clinical research with the intention to improve diabetes care in terms of maintaining targeted blood glucose levels, avoiding hypoglycemic episodes and complications and improving patient compliance and quality of life. METHODS: Based on the analysis of the databases found in the literature and the experience of our research team, nine important characteristics were identified as critical to an ideal diabetes database. The data for our database is collected using MÉRYkék glucometers, a device that meets all requirements of international regulations and measures blood glucose levels within the normal range with appropriate precision (10 %). RESULTS: Using the key characteristics defined, we were able to create a database suitable for the analysis of a large amount of data regarding diabetes care and outcomes. CONCLUSIONS: The MDD is a reliable and ever growing database which provides stable and expansive foundation for extensive clinical investigations that hold the potential to significantly influence the trajectory of diabetes care and enhance patient outcomes.

Risk Estimation of Gestational Diabetes Mellitus in the First Trimester.

CONTEXT: There is no early, first-trimester risk estimation available to predict later (gestational week 24-28) gestational diabetes mellitus (GDM); however, it would be beneficial to start an early treatment to prevent the development of complications. OBJECTIVE: We aimed to identify early, first-trimester prediction markers for GDM. METHODS: The present case-control study is based on the study cohort of a Hungarian biobank containing biological samples and follow-up data from 2545 pregnant women. Oxidative-nitrative stress-related parameters, steroid hormone, and metabolite levels were measured in the serum/plasma samples collected at the end of the first trimester from 55 randomly selected control and 55 women who developed GDM later. RESULTS: Pregnant women who developed GDM later during the pregnancy were older and had higher body mass index. The following parameters showed higher concentration in their serum/plasma samples: fructosamine, total antioxidant capacity, testosterone, cortisone, 21-deoxycortisol; soluble urokinase plasminogen activator receptor, dehydroepiandrosterone sulfate, dihydrotestosterone, cortisol, and 11-deoxycorticosterone levels were lower. Analyzing these variables using a forward stepwise multivariate logistic regression model, we established a GDM prediction model with a specificity of 96.6% and sensitivity of 97.5% (included variables: fructosamine, cortisol, cortisone, 11-deoxycorticosterone, SuPAR). CONCLUSION: Based on these measurements, we accurately predict the development of later-onset GDM (24th-28th weeks of pregnancy). Early risk estimation provides the opportunity for targeted prevention and the timely treatment of GDM. Prevention and slowing the progression of GDM result in a lower lifelong metabolic risk for both mother and offspring.

Additive damage in the thromboxane related vasoconstriction and bradykinin relaxation of intramural coronary resistance arterioles in a rodent model of andropausal hypertension.

Hypertension and andropause both accelerate age-related vascular deterioration. We aimed to evaluate the effects of angiotensin-II induced hypertension and deficiency of testosterone combined regarding the resistance coronaries found intramurally. Four male groups were formed from the animals: control group (Co, n = 10); the group that underwenr orchidectomy (ORC, n = 13), those that received an infusion of angiotensin-II (AII, n = 10) and a grous that received AII infusion and were also surgically orchidectomized (AII + ORC, n = 8). AII and AII + ORC animals were infused with infusing angiotensin-II (100 ng/min/kg) using osmotic minipumps. Orchidectomy was perfomed in the ORC and the AII + ORC groupsto establish deficiency regarding testosterone. Following four weeks of treatment, pressure-arteriography was performed in vitro, and the tone induced by administration of thromboxane-agonist (U46619) and bradykinin during analysis of the intramural coronaries (well-known to be resistance arterioles) was studied. U46619-induced vasoconstriction poved to be significantly decreased in the ORC and AII + ORC groups when compared with Co and AII animals. In ORC and AII + ORC groups, the bradykinin-induced relaxation was also significantly reduced to a greater extent compared to Co and AII rats. Following orchidectomy, the vasocontraction and vasodilatation capacity of blood vessels is reduced. The effect of testosterone deficiency on constrictor tone and relaxation remains pronounced even in AII hypertension: testosterone deficiency further narrows adaptation range in the double noxa (AII + ORC) group. Our studies suggest that vascular changes caused by high blood pressure and testosterone deficiency together may significantly increase age-related cardiovascular risk.

Vascular malformations and tumors of the hand: A therapeutical approach.

Background: Even though vascular anomalies of the hand are rare entities (7%), they are relevant regarding soft tissue mass differential diagnosis on the hand. 2 The majority of cases tend to be malformations, once denominated as deep soft tissue hemangiomas. 1 , 3 Due to evolving knowledge regarding vascular anomalies, the prognosis, guidelines regarding treatment and aftercare following therapy/surgery will be more accurate and detailed if the correct diagnosis is established. Methods: Retrospective data collection and analysis between 2008 and 2019, from the Orthopedic Department of Semmelweis University tumor registry. Comparison to the current literature (PubMed, Ovid). Study level of evidence III. Standardly distributed data with confidence level of 95%. Results: N = 16, average age of 34,2. 63,5% of lesions were digital. Hemangiomas accounted for 67%. The accuracy of clinical vs. histological diagnosis was 77%. Recurrences 25%. Variable follow up period. Conclusion: Clinical examination, radiological evaluation, patient history and fine needle biopsy are often accurate guides. Nevertheless in our study, histological analysis of the surgical biopsy was the most effective method in establishing a definite diagnosis. Conservative and watchful waiting approach are the first line, and when complemented with appropriate imaging, should suffice until absolute or relative operative indications are present.

Effects of Vitamin D on Fertility, Pregnancy and Polycystic Ovary Syndrome-A Review.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine reproductive disorders in women. Vitamin D deficiency is also quite common in this condition. The degree of vitamin D deficiency correlates with the severity of PCOS. Both male and female vitamin D levels play a role in fertility and affect the outcomes of in vitro fertilization (IVF). Moreover, fertility and IVF indicators are improved by vitamin D not only in healthy women but in those diagnosed with PCOS. Both vitamin D deficiency and PCOS increase pregnancy-related complications. Vitamin D supplementation and optimal vitamin D levels decrease both maternal and fetal risk for complications and adverse events. Furthermore, vitamin D supplementation may ameliorate or even prevent pregnancy-related reversible bone loss in mothers. This review emphasizes the roles of vitamin D deficiency and vitamin D supplementation and their correlation with PCOS regarding reproductive health.

Pediatric tracheal injuries: Report on 5 cases with special view on the role of bronchoscopy and management.

INTRODUCTION: The purpose of these case reports is to draw the attention to the difficulties of diagnosing trachea injuries in children, who are often part of a polytrauma scenario. MATERIALS: A retrospective multicenter analysis of 5 cases were analysed. The age of the children was between 1 and 16 years old. Injury mechanism was blunt thoracic trauma, misintubation and shot injury. RESULTS: Case No.1. a three-year-old child suffered a train accident. Resuscitation and decompression of the tension pneumothorax were performed. CT found a pneumomediastinum and bubbles along the trachea. Thoracolaparotomy was performed. Bronchoscopy could not rule out a tracheal injury. The child died of a cerebral edema. Case No. 2: a 13 month drowned and was resuscitated. A chest drain was inserted to treat the pneumothorax. CT revealed a pneumomediastinum, which was drained and a small tear of the trachea. Bronchoscopy was not preformed. Case No. 3: 9 year-old polytrauma patient was airlifted with bilateral mini thoracostomies and chest drains for pneumothorax. CT revealed bilateral pneumothorax and pneumomediastinum. The chest drains were repositioned oxygenation improved, but some ventilation difficulties remained. CT revealed pneumomediastinum and a tracheal injury. This was bridged by a tube, and the mediastinum drained. The ventilation difficulties were resolved. Case No. 4: an eight-year-old boy was shot on the neck. The region was explored surgically and the laceration of the trachea was sutured. Case No. 5: 12-year-old girl suffered blunt thoracic trauma. CT revealed bilateral pneumothorax and pneumomediastinum. Bilateral thoracic drainage was performed, some ventilation problems persisted. CT and fiberoscopy revealed a rupture of the trachea. Thoracotomy was performed and the laceration was closed. CONCLUSION: Pneumomediastinum and persistent ventilation difficulties should raise suspicion of a tracheal injury in a typical clinical scenario. Bronchoscopy is recommended for early diagnosis, despite the possibility of misdiagnosis. In certain cases CT scan only and close observation may be considered.

The Three Step Approach to the management of acute pediatric Monteggia lesions.

BACKGROUND: The literature places the occurrence of paediatric Monteggia lesions between 1.5% and 3% of all childhood elbow injuries. There are circumstances, which may make early correct diagnosis difficult. Failure to make an early correct diagnosis may have catastrophic consequences on joint range of motion in the chronic stage. The goal of this paper is to describe our three-step approach to the treatment of acute Monteggia lesions based on the stability and radiological appearance of the fracture dislocation, to give an overview of possible pitfalls and clinical and radiological signs that aid the diagnostic process. METHODS: Retrospective analysis of 23 patients treated for this type of injury at our Department over a period of 6 years was performed. Treatment options were 1. Closed reduction under image intensifier followed by immobilization in over the elbow cast, 2. Open reduction and intramedullary nailing with ESIN, or 3. Open reduction and plate osteosynthesis. Average follow-up was 37 months. In our Department we aim for definitive treatment of fracture-dislocations in children within the acute setting. In the 23 acute cases, the selected procedure-reduction+casting/reduction+ESIN/reduction+plating - was performed within 2 to 16 h of arrival. 10 patients were treated with reduction+casting, 10 with reduction+ESIN and 3 with reduction+plating. RESULTS: 21 patients were available for long-term follow-up. No nerve or tendon injuries or infections were observed in these cases. By managing the patients with the Three Step Method retaining the reduction was successful in all but one of our acute cases in the study period. Excellent range of motion was observed in all three groups. CONCLUSIONS: The Three Step Method allows for primary definitive treatment of these lesions with low complication rates and good range of motion result. Implementing the three step method in the acute phase helps avoid catastrophic consequences on joint range of motion in the chronic stage.

Effects of Testosterone Deficiency and Angiotensin II-Induced Hypertension on the Biomechanics of Intramural Coronary Arteries.

BACKGROUND: Andropause and hypertension also increase the risk of coronary artery damage. AIM: To investigate the effect of testosterone deficiency and hypertension on intramural coronary vessels. METHODS: 4 groups of 8-week-old Sprague-Dawley rats were studied: control male (Co, n=10), orchidectomized male (OCT, n=13), angiotensin (AII) hypertensive male (AII, n=10), and AII hypertensive and OCT (AII + OCT, n=8). Surgical orchidectomy was performed, and an osmotic minipump was inserted for chronic angiotensin II infusion (100 ng/min/kg). After 4 weeks, spontaneous tone and biomechanical properties of the intramural coronary resistance artery were investigated in vitro, by pressure microarteriography. OUTCOMES: Morphology and biomechanics of the intramural coronaries were evaluated: the outer diameter, wall thickness-to-lumen diameter ratio, and tangential wall stress in the contracted and relaxed states. RESULTS: The outer diameter was reduced in OCT and AII + OCT groups (on 50 mmHg 315 ± 20 Co; 237 ± 21 OCT; 291 ± 16 AII, and 166 ± 12 µm AII + OCT). The increased wall thickness-to-lumen diameter ratio resulted in lower tangential wall stress in AII + OCT rats (on 50 mmHg 19 ± 2 Co; 24 ± OCT; 26 ± 5 AII, and 9 ± 1 kPa AII + OCT). Spontaneous tone was increased in the hypertensive rats (AII and AII + OCT groups) (on 50 mmHg 7.7 ± 1.8 Co; 6.1 ± 1.4 OCT; 14.5 ± 3.0 AII, and 17.4 ± 4.1 % AII + OCT). CLINICAL IMPLICATIONS: Andropause alone can be considered as a cardiovascular risk factor that will further exacerbate vascular damage in hypertension. STRENGTHS & LIMITATIONS: A limitation of our study is that it was performed on relatively young rats, and the conclusions might not apply to coronary remodelling in older animals with slower adaptation processes. CONCLUSIONS: Testosterone deficiency and hypertension damage the mechanical adaptation of the vessel wall additively: double noxa caused inward eutrophic remodeling and increased tone. Jósvai A, Török M, Mátrai M, et al. Effects of Testosterone Deficiency and Angiotensin II-Induced Hypertension on the Biomechanics of Intramural Coronary Arteries. J Sex Med 2020;17:2322-2330.

Initiation of reticular and spider veins, incompetent perforantes and varicose veins in the saphenous vein network of the rat.

In an attempt to induce experimental varicosity, reverse perforant vein development was initiated in the rat leg by applying a chronic (14 and 32 weeks) partial stricture on the main branch of the deep femoral vein. At surfacing of the incompetent perforantes, typical reticular vein plaques and spider veins were identified by video-microscopy and quantitative histology. Deep vein blood was channeled by them into the saphenous vein system, the extra flow deforming these vessels, causing local dilations and broken course, even undulations of larger branches.

Papillary Endothelial Hyperplasia (Masson Tumor) of the Hand. Surgical and Pathological Consideration from Seven Cases Using New Vascular Markers.

Although papillary endothelial hyperplasia may occur at almost any site, one of the most common sites is the hand. It is generally regarded as a reactive vascular proliferation i.e. exuberant form of organizing thrombus. Diagnosis of Masson tumor can be challenging due to its close clinical, radiological and even histopathological resemblance to angiosarcoma. We present seven cases of Masson tumor of the hand; wanting to reveal its nature using new vascular markers and discuss the treatment options and expected outcomes, present clinical and radiological features that may aid diagnosis and also offer treatment plans. A multicenter retrospective study was performed between January 2014 and November 2019. Immunohistochemical stains of Glut1, WT1, ERG, CD31 and alpha smooth muscle actin (ASMA) were performed on each cases. We found seven cases during the examined period. 4 out of 7 cases were women. All lesions occurred in the hands. 3 out of 7 cases appeared in a previously present vascular malformation. All cases were treated with surgical excision and the diagnosis of papillary endothelial hyperplasia was made by histology. Pre-operative testing (radiograph/MRI/US/fine needle aspiration biopsy) did not suggest the diagnosis of Masson tumor; however, aspiration cytology could rule out malignancy. The proliferative endothelial cells proved to be Glut1 negative and WT1 positive and the accompanying pericytic cells were ASMA positive in all cases. Though Masson tumor is a rare vascular lesion in the hand among other vascular tumors, it should be considered in the differential diagnostics even in the case of previously existing vascular malformation. WT1 positivity of the endothelial cells and the accompanying pericytic cells raises the question whether the initially reactive endothelial proliferation may transform into a true benign vascular tumor.

[Treatment of De Quervain's tendinopathy with conservative methods]. / A De Quervain-féle tendinopathia kezelése konzervatív módszerekkel.

Introduction: De Quervain's tendinopathy affects the region of the wrist and the hand. Thumb motion becomes painful. This illness is caused by a degenerative process rather than inflammation. Primary treatment methods are splinting, taking non-steroid anti-inflammatory drugs and different physical therapeutic modalities, administration of a steroid injection into the tendon sheath or surgical release of the tendon sheath may be performed. Aim: The aim of the present study was to investigate whether conservative treatment complemented by eccentric training could provide an adequate alternative to the currently accepted treatment options. Method: The eccentric training lasted for 8 weeks (if necessary for 12 weeks). Following the introduction to exercises, patients (n = 9) repeated the training several times a day, which was controlled during weekly meetings. At the 1st, 8th and 12th meetings, inspection and the following measurements were performed: range of motion, muscle strength, evaluation and number of painful regions including the completion of patient questionnaires. Data were analysed with paired samples t-tests and repeated measures ANOVA. IBM SPSS Statistics 25.0 and Microsoft Office Excel Professional Plus 2016 programs were used. Results were regarded significant at level of p<0.05. Results: Significant improvements were found in the intensity of pain (Numeric Pain Rating Scale p = 0.005, n = 9) and in the functionality of the hand and wrist (Quick Disabilities of the Arm, Shoulder and Hand questionnaire part 1. p<0.001, part 2. p<0.001, Patient-Rated Wrist Evaluation questionnaire p<0.001; n = 9). Conclusion: With careful patient selection, conservative treatment complemented by eccentric training could be an alternative to current treatment options. Orv Hetil. 2020; 161(11): 419-424.

[Osteoid osteoma of the hand - Diagnostics and operative treatment]. / A kéz osteoid osteomáinak kivizsgálása és mutéti ellátása.

Introduction: Osteoid osteoma is a rare benign bone tumor displaying typical clinical symptoms and radiological signs in most cases. Characteristic symptoms are nocturnal pain alleviated by non-steroid antiinflammatory drugs. Radiological findings are also characteristic, the central osteolytic 'nidus' is surrounded by reactive sclerosis. These lesions are rare in the hand, typical symptoms may be absent, furthermore, atypical symptoms may occur. Characteristic radiographic signs may also be missing. Therefore, diagnosis may prove difficult. In the case of radiological/clinical suspicion, HRCT (high-resolution CT) is recommended. Aim: Our aim is to summarize the pathophysiology, occurrence and clinical features of these lesions and also the difficulties that accompany diagnosis on the hand. Treatment options will also be discussed. Method: Retrospective analysis was performed at Semmelweis University, Department of Orthopedics, between March 2014 and December 2018. Inclusion criteria were: patients who had undergone treatment for osteoid osteoma during this period. Data from the 6 patients who have undergone open surgery for osteoid osteoma of the hand will be presented as case reports. Results: During this period, a total of 112 patients were treated for osteoid osteoma at our Department, 8 lesions were found on the hand (7%). Among the cases presenting on the hand, typical nocturnal pain was absent in 3 cases, and in 1 case the pain did not respond to non-steroid antiinflammatory drugs. Open surgery and curettage was performed in 6 cases with good results. Conclusion: Osteoid osteoma on the hand is rare, typical symptoms may be missing, and atypical symptoms may occur. Radiographic findings may be nondescript, HRCT is recommended in the case of clinical suspicion. Performing radiofrequency ablation for osteoid osteoma of the hand may pose difficulties, curettage is the gold standard of treatment. Curettage alleviates symptoms well. Orv Hetil. 2020; 161(7): 263-268.

High pressure-low flow remodeling of the rat saphenous vein wall.

Objective To better understand factors that may play a role in the development of varicosities. Methods We induced combined flow-pressure disturbance in the saphenous system of the rat by performing chronic partial clipping of the main branch. Biomechanical and quantitative histological testing was undertaken. Results A rich microvenous network developed. Bloodflow decreased to 0.65 ± 0.18 µl/s (control side, 3.5 ± 1.4 µl/s) and pressure elevated to 6.8 ± 0.7 mmHg (control side, 2.3 ± 0.2 mmHg, p < 0.05). Involution of the wall and lumen was observed (16.5%, 28.7% and 35.5% reduction in outer diameter, wall thickness and wall mass respectively, p < 0.05). Elevated macrophage (CD68) and cell division (Ki67) activity was observed. Elastic tissue and smooth muscle actin became less concentrated in the inner medial layers. Conclusions Low-flow induced morphological shrinking of the lumen in veins may override pressure-induced morphological distension. Loosening of the force-bearing elements during flow-induced wall remodeling may be an important pathological component in varicosity.

Estrogen therapy may counterbalance eutrophic remodeling of coronary arteries and increase bradykinin relaxation in a rat model of menopausal hypertension.

OBJECTIVE: Hypertension causes adverse remodeling and vasomotor alterations in coronaries. Hormones such as estrogen may help counterbalance some of these effects. The aim of this study was to analyze the effects of ovariectomy and estrogen therapy in a rat model of menopausal hypertension induced by angiotensin II (AII). METHODS: We investigated diameter, tone, and mechanics of intramural coronaries taken from ovariectomized female rats (n = 11) that received chronic AII treatment to induce hypertension, and compared the results with those found in female rats that were also given estrogen therapy (n = 11). The "hypertensive control" group (n = 11) underwent an abdominal sham operation, and received AII. After 4 weeks of AII treatment, side branches of left anterior descendent coronary (approximately 200 µm in diameter) were isolated, cannulated with plastic microcannulas at both ends, and studied in vitro in a vessel chamber. The inner and outer diameter of the arteries were measured by microangiometry, and spontenuous tone, wall thickness, wall cross-sectional area, tangential stress, incremental distensibility, circumferential incremental elastic modulus, thromboxane agonist-induced tone, and bradykinin-induced dilation were calculated. RESULTS: In hypertension, intramural small coronaries show inward eutrophic remodeling after ovariectomy comparing with hypertensive controls. Estrogen therapy had an opposite effect on vessel diameter. Hormone therapy led to an increase in spontaneous tone, allowing for greater dilatative capacity. CONCLUSIONS: Estrogen may therefore be considered to counterbalance some of the adverse changes seen in the wall of intramural coronaries in the early stages of chronic hypertension.

Sex differences in the biomechanics and contractility of intramural coronary arteries in angiotensin II-induced hypertension.

BACKGROUND: It is well known that sex differences occur in both the pathogenesis and therapy of hypertension. A deeper understanding of the underlying processes may be helpful when planning a personalized therapeutic strategy. OBJECTIVE: In laboratory animal experiments, we studied the early mechanisms of vascular adaptation of the intramural small coronary arteries that play a fundamental role in the blood supply of the heart. METHODS: In our study, an osmotic minipump was implanted into 10 male and 10 female Sprague-Dawley rats. The pump remained in situ for 4 weeks, infusing a dose of 100 ng/kg/min angiotensin II acetate. Four weeks later, the animals were killed, and the intramural coronary arteries from the left coronary branch, which are fundamentally responsible for the blood supply of the heart, were prepared. The pharmacologic reactivity and biomechanical properties of the prepared segments were studied in a tissue bath. RESULTS: The relative heart mass and vessel wall thickness were greater in females than males (0.387 [0.009] g/100 g vs 0.306 [0.006] g/100 g body weight; 41.9 [4.09] µm vs 33.45 [3.37] µm on 50 mm Hg). The vessel tone and vasoconstriction in response to thromboxane agonists were, however, significantly more pronounced in males. The extent of relaxation in response to bradykinin was also greater in females. Although we observed inward eutrophic remodeling in females, an increase in wall stress and elastic modulus dominated in males. CONCLUSION: The early steps of angiotensin II-dependent hypertension evoked very different adaptation mechanisms in males and females.