Purpose. We describe a modified trabeculectomy technique in which the iris is used to prevent fibrosis of the scleral flap. Material and Methods. A retrospective case series of patients with medically uncontrolled open angle glaucoma underwent trabeculectomy. Instead of performing a classical iridectomy, the iris was used as spacer underneath the scleral flap. Postoperative management was identical to classical trabeculectomy, with suture removal and needling if necessary. Five of the patients underwent simultaneous phacoemulsification through a separate temporal corneal incision. Patients should have two-year follow-up. Results. Data of ten patients were analysed, two had a previous failed trabeculectomy, two had LTP, and one had a corneal transplantation. In 3 patients MMC 0,1 mg/mL was used. After one and two years mean IOP was, respectively, 13,1 and 12,1 mmHg. IOP ≤ 16 mmHg was reached in 90% of patients without pressure lowering medication. No major complications were seen; no abnormal inflammatory reaction and no deformation or dislocation of the pupil occurred. Conclusion. By using the iris from the iridectomy as spacer under the scleral flap, fibrosis of the scleral flap is no longer possible. This iridenflip trabeculectomy technique gives an excellent complete success rate (IOP ≤ 16 mmHg) of 90%. A larger study is currently being done. Surgical treatment of COAG can be very effective in reducing IOP; however success ratios are still not optimal. Trabeculectomy is the most frequently performed filtering procedure and many variants have been developed, but they often face failure due to conjunctival or scleral fibrosis . PostopeWe describe a technique in which the iris of the iridectomy is used as a spacer to prevent fibrosis of the scleral flap.Retrospective case series was as follows. Eleven consecutive patients with medically uncontrolled open angle glaucoma underwent trabeculectomy with the iridenflip technique. Outcome measures were IOP and postoperative complications. Patients should have at least two years of follow-up. There were no other exclusion criteria.Trabeculectomy technique was similar to our classical technique, with the only difference that the iris from the iridectomy was not discharged but used as spacer underneath the scleral flap.Trabeculectomy was performed under retrobulbar anaesthesia. After a fornix based conjunctival flap, a rectangular scleral flap of 3 by 2,5 mm was made. A second triangular scleral flap is prepared up to Descemet's membrane and is removed completely including the trabeculectomy. Instead of performing a classical iridectomy, an angle based V-shaped iris incision is made. The iris base remains attached while the iris triangle is flipped onto the sclera. The length of the iris flap should be slightly longer than the scleral flap. The pigmented posterior iris epithelium is removed by gently touching it with a sponge. The scleral flap is closed with 2 releasable sutures' nylon 10/0 according to Khaw's technique [Postoperative treatment consisted of atropine 2% 3 times daily and tobramycin combined with dexamethasone 4 times daily.Postoperative management was similar as in classical trabeculectomy. Patients were seen at day 1, every week for 5 weeks, and then after 2 weeks and every 3 months thereafter. If IOP was too high manual pressure was applied to the eye to stimulate evacuation of aqueous or viscoelasticum towards the bleb. Suture removal was performed if pressure remained above 15 mmHg after one week or after 1 month in all patients.Topical steroids were tapered slowly over 3 to 4 months if pressure was good or increased if the bleb vascularisation increased or bleb size diminished or if pressure raised above 15 mmHg. Atropine was stopped after 2 weeks, unless there was persistent hypotony.Subconjunctival 5-FU injection was planned if conjunctival corkscrews vessels were seen.Complete success rate was defined as IOP ≤ 16 mmHg without any topical or systemic pressure lowering medication.Eleven patients with COAG underwent trabeculectomy with the iridenflip technique. Five of them had a combined phacotrabeculectomy. None of them had a narrow angle. One patient was lost to follow-up after 5 months, with a pressure of 10 mmHg, and was excluded.Ten patients were included in the analysis. Patient characteristics are shown in Male/female ratio was 1/1 and age ranged from 52 to 85 years .All patients were on topical pressure lowering medications, ranging from 1 to 4 (mean of 2.7 medications). Visual field MD defects ranged from 1,5 to −22,8 dB . Two patients had a previous failed trabeculectomy and two had LTP. One patient had a history of corneal transplantation.In 3 patients (30%) MMC 0,1 mg/mL was applicated during 1 minute because of a scarred conjunctiva or a low target pressure.Visual acuity was stable or increased in the combined procedures.Postoperative complications are shown in One patient had a wound leak on the first day, which did not heal with a contact lens and was closed by an additional suture. One patient had hypotony with choroidal effusion in one quadrant the first 2 weeks, which disappeared spontaneously. One patient had a small hyphema the first 2 weeks.In one patient with a low target pressure a needling revision with MMC was performed after 7 weeks because of IOP of 18 mmHg.5-FU was never needed.No late complications were seen. No abnormal inflammatory reaction and no deformation or dislocation of the pupil occurred . The pupAfter one year mean pressure was 13,1 mmHg, nine patients had IOPs ranging from 10 to 16 mmHg and one patient had an IOP of 19 mmHg .A pressure of 16 or lower was reached in 90% of patients without any pressure lowering medication after one year. In 70% IOP was even 14 or lower without medication .After two years mean pressure was 12,1 mmHg, ranging from 6 to 16 mmHg, with identical success rates.The initial results of this iridenflip trabeculectomy technique are very encouraging.Our small series demonstrated a complete success ratio of 90% in achieving IOP ≤16 mmHg after one and two years and in 70% IOP was ≤14 mmHg. Mitomycin C was used in 30% of the patients.Comparing trabeculectomy outcomes between different studies is difficult due to a variety in defining success rates and use of antimetabolites.n = 18) and 33% after phacotrabeculectomy (n = 15) without antimetabolites with a mean follow-up of 22,5 months.The trabeculectomy outcome study group  reportedOur complete success ratio can compete with the qualified success (with medication) of some larger studies. In the trabeculectomy arm of the TvT study  they repBut we like to stress that our series of 10 patients is too small to draw conclusions on efficacy.Current trabeculectomy technique still faces failure due to conjunctival or scleral fibrosis. It is known from older reports of the iridencleisis procedure that iris tissue can provide a long lasting fistulisation through the sclera , 7. AfteFollowing these first 10 cases, no abnormal inflammation or other problems were seen, compared to classical trabeculectomy. We had no higher incidence of postoperative manipulations. In one patient a needling revision was necessary in order to achieve a low target pressure.This technique is completely different from the old iridencleisis technique.In the original Holth's iridencleisis the iris prolapsed through the sclerotomy and was grasped with two forceps at the pupil and torn . The twoIn later modifications only the peripheral iris was prolapsed and incarcerated in the sclerotomy , leavingThe major drawback of all techniques was a complete distortion of the pupil with pear shaped corectopia pointing towards the 12 o'clock position, often with an upward displacement of the pupil. In case the iris sphincter was completely sectioned it resulted in a superior coloboma .In all our cases the pupil was round and well centred, with normal pupil reflex. When looking with the slit lamp an iridectomy is visible, but the deference with a classical iridectomy cannot be seen. Only with gonioscopy the iris base can be seen turning into the trabeculectomy window.A second reason why iridencleisis may have fell out of use is the possible risk of sympathetic uveitis, although only a total of 4 cases of sympathetic ophthalmia following iridencleisis have been reported . In the In our series we did not encounter any iritis or uveitis. In view of this historical threat of sympathetic ophthalmia, we reduce the amount of pigmented uveal tissue below the conjunctiva, by gently removing the posterior layer of the iris epithelium. The second reason to remove the pigmented layer was to avoid postoperative spread of these pigmented cells below the conjunctiva due to the aqueous flow. This can create a visible pigmentation which might be mistaken for a subconjunctival nevus or melanoma.In this study the iris from the partial iridectomy was used as spacer underneath the scleral flap, in order to prevent fibrosis of this scleral flap. The data show that no major complications were observed within the short observation period of 2 years.A major limitation of the study is the small number of patients and the absence of a control group. A larger RCT is needed to substantiate the alleged benefits.


Objective. To analyze the clinical characteristics of inpatients with anaphylaxis and the factors that influenced those characteristics. Methods. Using the patient records from 1990 to 2013 from three highly ranked Chinese hospitals, we retrospectively analyzed the characteristics of 108 inpatients with anaphylaxis (not anaphylaxis admitted). Results. The mean patient age was 42 ± 20 years old and male-to-female ratio was 1 : 1.3. The number of patients with anaphylaxis increased gradually, and cases diagnosed after 2005 accounted for 68.5% of the 108 total cases. The most common trigger was medications. The most common clinical manifestations included cutaneous, nervous, respiratory, circulatory, and digestive signs and symptoms. Male patients were more likely to experience loss of consciousness. Multisystem involvement was more likely to develop in patients with low BP, whereas it was uncommon in those with anaphylaxis induced by antibiotics or anesthetics. Epinephrine was used as the first-line treatment for 56 cases. Conclusions. Inpatient with anaphylaxis was more common in female patients and the number increased gradually during the study period. The most common trigger was medications. Patients with low BP were prone to having multisystem involvement, whereas the cases of anaphylaxis induced by antibiotics and anesthetics were less likely to involve multiple organ systems. Anaphylaxis is a severe and life-threatening allergic reaction that involves multiple organ systems or the whole body and has an incidence rate of 0.05%–2% . Acute eA total of 108 patients were diagnosed with anaphylaxis from 1990 to 2013 at the Peking Union Medical College Hospital (42 cases) and Peking University First Hospital (22 cases) and from 1993 to 2013 at the General Hospital of the Chinese People's Liberation Army (44 cases).In this retrospective study, all existing records were analyzed retrospectively and anonymously. We selected patients by discharge diagnosis codes; those admitted for anaphylaxis were excluded. We summarized the general patient condition, clinical manifestations during attacks, and factors that influenced the manifestations, including the relationships between gender, age, etiology, and underlying diseases with the laboratory and clinical manifestations of anaphylaxis and among clinical manifestations, the relationship between blood pressure and multisystem involvement. The study had been approved by ethics committee.Based on the criteria of the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the Joint Council of Allergy, Asthma and Immunology (JCAAI) , anaphylThe clinical presentations of anaphylaxis mainly involve the skin, respiratory tract, digestive tract, circulatory system, and nervous system. Patients were divided into 2 groups, one with at least 3 systems involved and the other with only 1 or 2 systems involved. The blood pressure and laboratory test results obtained during the episodes and during baseline conditions (times when the patients were not experiencing anaphylaxis attacks) were compared. Routine laboratory tests were conducted using an automatic biochemical analyzer and an automatic hematology analyzer.t-tests were applied to compare blood pressure and heart rate during episodes and during baseline conditions. Data that did not fit a normal pattern of distribution were expressed as medians . Among independent samples, normally distributed data were analyzed using a t-test and abnormally distributed data were analyzed using a rank-sum test. Constituent ratios were compared using the chi-square test. P values <0.05 represented statistically significant differences.The data were all tested for normal distributions. Normally distributed data were expressed as means ± standard deviation, and paired-sample The 108 patients in this study were 42 ± 20 years old (range: 3–76 years), including 46 males and 62 females .Among the anaphylaxis cases, 42 were inpatients from Peking Union Medical College Hospital, 44 were from the General Hospital of the Chinese People's Liberation Army, and 22 were from Peking University First Hospital. Anaphylaxis cases accounted for 0.005% of the 827,791 and 0.003% of the 786,732 inpatients were treated at the Peking Union Medical College Hospital and Peking University First Hospital, respectively, from 1990 to 2013, and 0.006% of the 796970 at the General Hospital of the Chinese People's Liberation Army from 1993 to 2013.The cases were 7, 15, 11, 30, and 45 during 1990–1994, 1995–1999, 2000–2004, 2005–2009, and 2010–2013, so the incidence was 0.005%, 0.006%, 0.003%, 0.005%, and 0.004%, respectively.P < 0.01) and the diastolic pressure decreased from 71.6 ± 13.6 mmHg during baseline conditions to 33.9 ± 21.4 mmHg during episodes (P < 0.01). Baseline heart rate records were available for all of the patients (81 ± 13 bpm), and the heart rates during episodes were recorded for 78 patients (107 ± 38 bpm) and were found to be significantly increased (P < 0.01).We evaluated the blood pressure and heart rate during anaphylaxis attacks. Baseline blood pressure was recorded for 105 cases. Blood pressure during attacks was recorded for 102 cases, of which 20 were unobtainable (systolic and diastolic pressures were both recorded as 0 mmHg). The systolic pressure decreased from 117.4 ± 13.8 mmHg during baseline conditions to 54.3 ± 31.9 mmHg during episodes (The cause of anaphylaxis was unclear for 4 cases (3.7%). In 97 cases (89.8%), anaphylaxis was presumably triggered by medications, specifically antibiotics in 32 cases (29.6%)—including penicillin, ciprofloxacin, cefoperazone sulbactam, cefmetazole, cravit, or cefaclor; contrast media in 18 cases (16.7%); chemotherapy drugs in 12 cases (11.1%)—including L-asparaginase, sulfur hexafluoride, and cisplatin; anesthetics in 8 cases (7.4%); nutritional support in 7 cases (6.5%); blood products in 6 cases (5.6%); antipyretic analgesics in 4 cases (3.7%); Chinese patent medicines in 3 cases (2.8%); a glucocorticoid in 1 case (0.9%); a vaccine in 1 case (0.9%); and other drugs in 5 cases (4.6%). In the remaining 7 cases, the trigger of anaphylaxis was smell in 1 case (0.9%) and food in 6 cases (5.6%), such as steamed bun of Chinese chive, protein powder, peanut, snapping turtle, wheat, and lactic acid milk biscuit. The symptoms of anaphylaxis developed immediately or within 6 hours after allergen exposure.Twenty-four patients experienced intraoperative anaphylaxis, including 11 during gynecologic surgery, 3 during otorhinolaryngologic surgery, 2 during pancreatic surgery, 2 during urologic surgery, 2 during cardiac surgery, and 1 each during thyroid, ophthalmic, breast, and gallbladder surgeries. Severe allergic reactions to chemotherapy drugs, antibiotics, anesthetics drugs, and nutritional support were detected in 4 cases, including 2 cases caused by blood transfusion, 1 caused by hemostatic drugs, and 1 caused by glucocorticoids. A history of food and/or drug allergies was positively reported in 28 patients and was not reported for the other 80 patients. Eight patients had a history of acute urticaria, bronchial asthma, or allergic rhinitis.Clinical manifestations were presented as follows in the 108 patients: 78 developed skin signs (72.2%), mainly rashes, itching, wheals, redness, and swelling; 59 had nervous system signs (54.6%), primarily loss of consciousness and syncope; 57 had respiratory signs (52.8%), mainly shortness of breath, dyspnea, and wheezing in all areas of the lungs; 45 had circulatory signs (41.7%), including pale face, palpitation, excessive sweating, lip cyanosis, and dizziness; and 41 had gastrointestinal signs (38.0%), including nausea, vomiting, abdominal pain, diarrhea, and fecal incontinence. Rashes, dyspnea, and loss of consciousness were the most common signs of anaphylaxis .P < 0.05), was significantly lower in patients with dyspnea compared with those who did not have dyspnea , and was also significantly lower in patients presenting loss of consciousness compared with those who did not present this sign .The relationship between gender and the most common clinical manifestations was as follows: the female-to-male ratio of patients who developed rashes was higher than that of patients with no rash .The relationship between blood pressure and the most common clinical manifestations was as follows: blood pressure was unobtainable in 20 cases, of which 11 (55.0%) had rashes and 11 (55.0%) had dyspnea, neither of which were significantly different from the percentages of the patients with obtainable blood pressure (62.9% and 43.8%); of the patients with unobtainable blood pressure, 55.0% experienced a loss of consciousness, which was significantly higher than that in patients with obtainable blood pressure , so did the decrease of eosinophil percentage (P = 0.000). A significant increase was detected in the blood glucose levels (P = 0.000), but not in the alanine transaminase, total bilirubin, creatinine, or blood urea nitrogen levels. Serum potassium and calcium levels both decreased during anaphylaxis , while no significant difference was observed for serum sodium or chloride levels.As shown in Patients were mainly treated with epinephrine and glucocorticoids, which alleviated the anaphylaxis condition in minutes or a few days. Epinephrine, glucocorticoids, and antihistamine were received among 56, 94, and 25 patients, respectively. Improvement or recovery was observed in all cases except for 6 deaths (5.6%). In these 6 patients, who were 43 ± 20 years old, 5 had visited one of the 3 hospitals in this study during the previous 10 years, 2 developed anaphylaxis during an operation, and 1 had a history of bronchial asthma. All episodes were triggered by medication, including 2 by antibiotics, 2 by chemotherapy drugs, 1 by a nutritional supplement, and 1 by a glucocorticoid; 6 patients experienced loss of consciousness and 3 patients had multisystem involvement.Anaphylaxis is a severe, rapidly progressing, systemic allergic reaction, usually with multisystem involvement, and is life-threatening if not immediately treated. The patients in this study all had acute onset after contact with or exposure to an allergen immediately or within 6 hours and presented with cutaneous, respiratory, circulatory, gastrointestinal, or nervous symptoms and signs. Patients experienced significant drops in blood pressure compared to baseline conditions, leading to a definitive diagnosis of anaphylaxis according to the criteria of the AAAAI, ACAAI, and JCAAI (revised in 2010) .According to Lieberman , the incP < 0.01), which might have resulted from increased vascular permeability or vascular smooth muscle relaxation induced by histamine release [P < 0.01), which might be caused by the decrease in the effective blood volume or by accelerated diastolic depolarization of the sinoatrial node induced by histamine-H1 receptor interactions [Women are affected more often than men . In the  release . Heart rractions .Identifying the cause of anaphylaxis is crucial for the targeted prevention of episodes, and medications were by far the most common cause , 11. ExcThe most common clinical manifestation of anaphylaxis is on the skin, including urticaria and angioedema, which are observed in 85%–90% cases of anaphylaxis; the most common respiratory sign is edema of the upper respiratory tract, observed in 50%–60% cases; 25%–30% cases present gastrointestinal signs, including nausea, vomiting, diarrhea, and cramp-like abdominal pain; 30%–35% cases have dizziness, syncope, and a blood pressure drop; and a few patients present headache, substernal chest pain, or epileptic seizures [Respiratory signs and loss of consciousness were more often observed in male patients. Because the patients who experience a blood pressure drop are more likely to develop circulatory and neurological signs, lower diastolic and systolic pressures are correlated with a higher possibility of multisystem involvement. Intraoperative anaphylaxis is seldom associated with multisystem involvement, most likely because under general anesthesia the occurrence of anaphylaxis is usually detected based on a blood pressure drop and reduced oxygen saturation, as shown on monitors, or by a wheal-like rash over the torso or limbs observed after removing sterile drapes. Anaphylaxis in these cases is not based on patient-reported chest distress, shortness of breath, dyspnea, abdominal pain, nausea, vomiting, dizziness, or syncope, in contrast to patients with full consciousness.Increased white blood cell counts, neutrophil percentages, and blood glucose levels were observed in this study in anaphylaxis patients, which is presumably the result of stress and elevated blood catecholamine levels. A reduction in serum potassium levels during anaphylaxis attacks was also noticed, likely because high catecholamine levels would induce potassium transport into the cells and produce a transient decrease in serum potassium . The redThe first choice treatment for anaphylaxis is the timely administration of epinephrine , 18, 19.This is, as far as we know, the first inpatient anaphylaxis study among three highly ranked hospitals in China. In this study, we had a few limitations, which were lack of tryptase and sIgE detection. Anaphylaxis is a clinical diagnosis that builds on the clinical criteria . RetrospIn conclusion, the anaphylaxis inpatients studied in the 3 hospitals were more common in female patients. The number of inpatients with anaphylaxis exhibited a rising trend over the study period. During anaphylaxis attacks, the patients presented significantly decreased blood pressure and increased heart rates. The most common causes were drugs, especially antibiotics. The most common clinical manifestations were skin signs; respiratory, neurological, circulatory, and gastrointestinal signs were also common. Male patients were more prone to develop respiratory signs and lose consciousness. The patients presenting a drop in blood pressure during anaphylaxis attacks were more likely to have multisystem involvement, whereas those patients with anaphylaxis induced by antibiotics or anesthetics were less likely to have multisystem involvement.


SHRs) are more sensitive to chronic angiotensin (Ang) II‐induced hypertension compared with female rats. This study was designed to test the hypothesis that anesthetized male SHRs are also more responsive to acute Ang II‐induced increases in blood pressure and renal hemodynamic changes when compared with female SHRs. Baseline mean arterial pressure (MAP) was higher in male SHRs than in female SHRs . Acute intravenous infusion of Ang II (5 ng/kg/min) for 60 minutes significantly increased MAP to 148 ± 2 mmHg in male SHRs (P < 0.05) without a significant change in MAP in female SHRs. Baseline glomerular filtration rate (GFR) was also higher in male SHRs than in female SHRs . Ang II infusion for 60 min significantly decreased GFR in male SHRs  without significant changes in urine flow rate, sodium, or chloride excretion. In contrast, Ang II infusion increased GFR in female SHRs . The increase in GFR upon Ang II infusion in female SHRs was associated with increases in urine flow rate (4.3 ± 0.3 to 7.1 ± 0.9 μL/min), sodium excretion (0.16 ± 0.04 to 0.4 ± 0.1 μmol/min), and chloride excretion . These findings support the hypothesis that there is sex difference in response to acute Ang II infusion in SHRs with females being less responsive to Ang II‐induced elevations in blood pressure and decreases in GFR relative to male SHRs.We previously reported that male spontaneously hypertensive rats ( The renin–angiotensin system (RAS) plays a critical role in the regulation of fluid homeostasis and arterial pressure  are a genetic model of essential hypertension, and there are well‐established sex differences in the RAS in SHRs  and approved and monitored by the Georgia Regents University Institutional Animal Care and Use Committee. Rats were maintained at the Georgia Regents University animal care facility for 1 week before the study for acclimation purposes. Rats were housed in temperature‐controlled conditions with a 12 h:12 h light–dark cycle. Pilot experiments were performed to determine a dose of Ang II  that produces minimal change in blood pressure in male and female SHRs using graded bolus doses of Ang II . Separate sets of male and female SHRs (n = 7–8/group) were used to determine the effects of acute Ang II on blood pressure, glomerular filtration rate (GFR), electrolyte excretion, and urine flow rate.Twelve‐ to thirteen‐week‐old male and female SHRs were used in this study . All experiments were conducted in accordance with the National Institutes of Health  and placed on a servo‐controlled heating table to maintain rectal temperature constant at 37°C. Using polyethylene (PE)‐200 tubing, a tracheostomy was performed to allow unobstructed breathing. A PE catheter (PE‐50) was inserted into the carotid artery for measuring mean arterial pressure (MAP) using a PowerLab data acquisition system . The right jugular vein and femoral vein were cannulated using PE‐50 catheters for continuous infusion of maintenance fluids (6.2% BSA in PBS at 1.8 mL/h) or fluorescein isothiocyanate‐inulin , respectively. Another PE catheter (PE‐90) was placed into the urinary bladder for urine collection. After a 60‐min equilibration period, a 30‐min baseline urine collection period was begun that included a blood sample taken at the midpoint of the period to determine hematocrit values. Following the first 30‐min baseline urine collection, Ang II was infused at a dose of 5 ng/kg/min for 1 h. Based on pilot studies indicating an increase in MAP in male SHRs following a bolus dose of Ang II at 10 ng/kg  were infused with vehicle (6.2% BSA in PBS at 1.8 mL/h) and fluorescein isothiocyanate‐inulin  to exclude the possibility that changes in hemodynamics in SHRs are due to volume expansion.Additional anesthetized male and female SHRs All the data are presented as mean ± SEM. Student's HRs Fig. . EvaluatPreliminary studies were performed to determine a dose of Ang II that produced a minimal change in arterial pressure in male and female SHRs to exclude changes in blood pressure as a variable in the impact of acute Ang II on renal hemodynamic responses. As shown in Figure P = 0.05; effect of Ang II infusion for 30 min, P = 0.001; effect of Ang II infusion for 60 min, P = 0.001; interaction, P = 0.05). There was no difference in HR between male and female SHRs prior to Ang II infusion, and Ang II did not alter HR in either sex . Female SHRs also had a lower baseline urine flow rate than males consistent with their lower GFR .Baseline GFR was significantly greater in male SHRs than in female SHRs Fig. A. InfusiP > 0.05; effect of Ang II infusion for 30 min in female SHRs, P > 0.05; effect of Ang II infusion in female SHRs for 60 min, P = 0.04; interaction, P = 0.1 and two‐way ANOVA for chloride excretion: effect of sex, P > 0.05; effect of Ang II infusion for 30 min in female SHRs, P > 0.05; effect of Ang II infusion in female SHRs for 60 min, P = 0.01; interaction, P = 0.1). Neither sex nor Ang II infusion significantly altered potassium excretion or hematocrit values . There were also no significant changes in HR, electrolyte excretion, or hematocrit values in male or female SHRs after vehicle infusion (data are not shown).To exclude the possibility that differential renal responses to Ang II infusion between male and female SHRs were due to volume expansion, male and female SHRs were also infused with vehicle (6.2% BSA in PBS at 1.8 mL/h) for 1 h. Infusion of vehicle did not change MAP, GFR, or urine flow rate in male or female SHRs compared with their baseline values  do sex differences in blood pressure responses to chronic Ang II simply reflect males reaching a higher end blood pressure than females or are there inherent differences in how blood pressure increases following exposure to Ang II; and (2) based on the central role of the kidney in the long‐term control of blood pressure, are there sex differences in renal hemodynamic responses to acute Ang II? The current study extends previous findings by reporting that female SHRs are less sensitive to acute Ang II‐induced changes in MAP and GFR relative to males. Based on the sensitivity of the kidney to Ang II, attenuated increases in renal hemodynamic responses to Ang II infusion in the female likely offer an additional mechanism by which Ang II‐induced hypertension is reduced in females relative to males.Clinical and experimental studies suggest that males are more sensitive to chronic Ang II‐induced elevations in blood pressure than females  in female SHRs attenuates the hypertensive response to chronic Ang II infusion (Sullivan et al. A limitation of the current study is that the dose of Ang II chosen for the constant infusion period was outside the range of Ang II doses used in the pilot study, and bolus injections were used in the pilot rather than constant infusions. A lower dose was chosen to utilize a dose of Ang II that did not result in increases in blood pressure, with the intent of avoiding a confounding effect of blood pressure on renal hemodynamic responses. However, as noted above, even this low dose of Ang II increased blood pressure in male SHRs over the 60‐min infusion period. An alternative approach for the pilot studies would have been to infuse even lower doses of Ang II at steady rates with step‐wise increases. Regardless, our design did allow us to select a dose of Ang II that resulted in sex‐specific effects on blood pressure and renal hemodynamic responses.Close to half of hypertension population are women, yet the majority of basic science studies continue to focus on males despite growing evidence that suggests that the pathways regulating cardiovascular and renal function are distinct in males and females. There are conflicting data in the literature regarding whether there is sex difference in response to Ang II infusion clinically. Although Miller et al. (Miller et al. None declared.


AB  during both pre-stimulation and stimulation, but the relative increase was similar during the stimulation period. Changes in PCAv during stimulation were mitigated in the SCI group (6% ± 6%) vs. AB . Heart rate and end-tidal carbon dioxide responded similarly between groups. Conclusions: Clearly, NVC is impaired in those with SCI. This study may provide a link between poor perfusion of the posterior cerebral region (containing the medullary autonomic centres) and autonomic dysfunction after SCI.Purpose: To compare neurovascular coupling in the posterior cerebral artery (PCA) between those with spinal cord injury (SCI) and able bodied (AB) individuals. Methods: A total of seven SCI and seven AB were matched for age and sex. Measures included PCA velocity (PCAv), beat-by-beat blood pressure and end-tidal carbon dioxide. Posterior cerebral cortex activation was achieved by 10 cycles of (1) 30 s eyes closed (pre-stimulation), (2) 30 s reading (stimulation). Results: Blood pressure was significantly reduced in those with SCI   Spinal cord injury (SCI) leads to not only devastating paralysis, but also serious cardiovascular complications ,2,3,4. RCerebrovascular reserve is an important marker of the relationship between blood pressure and cognitive function. A reduction in cerebrovascular reserve has been associated with impaired neurovascular metabolic coupling (NVC) and reduced cognitive function . Neurovai.e., anterior spinal artery, posterior inferior cerebellar artery) deriving from the vertebral arteries. As the posterior cerebral artery (PCA) arises (in the majority of people) from the vertebral arteries, an evaluation of PCA function in those with SCI is pertinent to our understanding of autonomic dysfunction (as it relates perfusion of the autonomic brain centre) in this population. The medullary region of the brainstem is the primary centre of autonomic control. Poor cerebrovascular regulation after SCI in the medullary region may exacerbate blood pressure and autonomic instability commonly found in this population ,20. Blooi.e., >T2) by quantifying NVC in this population as compared to age- and sex-matched able-bodied controls (AB). Due to a combination of low resting blood pressure and impaired sympathetic control of cerebral blood vessels , we hypothesized that individuals living with SCI would have impaired NVC as compared to able-bodied controls. Our study aimed to measure PCA regulation in those with high- level SCI  participated in this study (n = 7). The control group (AB) was comprised of 7 participants  matched for age (SCI: 33 ± 12 vs. AB: 31 ± 11 years) and sex. Participants were similar for height (SCI: 173 ± 7 vs. AB: 173 ± 11 cm), weight (SCI: 66 ± 12 vs. AB: 69 ± 15 kg) and body mass index (SCI: 22 ± 3 vs. AB: 23 ± 3 kg/m2). Seven individuals  with SCI , or moved the mechanized hospital bed into the seated position (n = 2). For AB participants, testing took place in the morning within a dedicated research space in the same location. Both AB and SCI rested in the seated position for 30 min prior to starting the NVC procedure. Our team arrived and transferred the participants to their wheelchair if they were capable ) from a leak-free mask, and non-invasive beat-to-beat blood pressure ) were collected at 1 kHz per channel through an analog-to-digital converter . Electrocardiography, expired end-tidal carbon dioxide . The PCA blood velocity (PCAv) was collected and recorded through the analog-to-digital converter. The PCA was confirmed using ipsilateral carotid compression that causes an increased velocity in the PCA and a velocity reduction in both the middle and anterior cerebral arteries .2.The NVC procedure included 10-repeated bouts intended to activate the visual cortex. Each bout consisted of a 30 s pre-stimulation period where the participant sat quietly with eyes-closed, followed up a 30 s long stimulation period where the participants read from a general interest magazine. The same magazine was used for all participants. The participants were provided an auditory stimulus every 30 s with either the command “eyes open” or “eyes closed” while a research assistant held the magazine at an appropriate height and distance. One practice trial occurred prior to the 10 cycles. Using the electrocardiogram to gate the extraction, beat-to-beat heart rate, peak systolic and end diastolic blood pressure, as well as peak and end diastolic PCAv were recorded continuously. Also, the peak expired carbon dioxide value was exported from each breath to measure ETCO2) values were extracted (using a customized Microsoft Excel program) and evaluated statistically. All comparisons were evaluated using an independent t-test between groups with alpha set to 0.05. Data are presented as means ± SD. All values were interpolated using cubic spline at 0.2 Hz. All 10 trials were aligned according to the initiation time (eyes open) and averaged to generate one response slope per subject. Maximum and minimum . The difference in blood pressure between the two groups remained throughout the stimulation period; however, the change occurring from pre-stimulation to stimulation was similar  and SCI (37 ± 10 cm/s) participants . The incThis is the first study to report NVC in SCI. We have shown that NVC is impaired in those with SCI. Specifically, the PCAv response to posterior cortex stimulation is mitigated in those with SCI. As the PCA is directly downstream from the vertebral arteries (which provide the majority of blood flow to the medullary autonomic centres in the brain) this finding may have important implications for autonomic dysfunction after SCI . These fi.e., increased cerebrovascular conductance in order to maintain PCAv during hypoperfusion) in our SCI group impaired cerebrovascular reserve and severely disrupted the ability of the brain to further increases conductance in response to increased metabolic stimuli. In other words, it may be that the perfusion pressure in those with SCI is too low to make use of small and subtle changes in vasomotor tone that occur during increased cerebral metabolic demand [We are not aware of any studies examining PCA blood flow in those with SCI. Similar resting PCAv in both groups suggests the static cerebral autoregulatory capacity of the PCA is intact in those with SCI. The 29% ± 12% increase in the PCA in AB is comparable to that reported elsewhere using a similar stimulation task . The lacc demand ,24. Indec demand . In contc demand . Personsc demand . This lec demand . The ina1 to T4 spinal nerves [1 level in all but one case. Prior work in those with autonomic failure supports this contention, showing a similar blood pressure response to cognition with a mitigated cerebral blood flow response [Alternatively, sympathetic vasomotor control in the brain is achieved through the superior cervical ganglion which receives input from the Tl nerves . It is lresponse . AccordiAn important limitation of this study arises from the use of trancranial Doppler for estimation of blood flow. Because of the attenuation of the ultrasound signal when travelling through the skull, transcranial Doppler can only estimate flow velocity. As per convention and supported by evidence in humans, using hypovolemic stimulus causes no change in middle cerebral artery diameter; we infer a constant diameter of the PCA ,29. i.e., impaired blood flow delivery influencing impaired medullary function). These findings have important implications for addressing the altered cerebrovascular control seen in SCI. Interventions (such as exercise training) that are known to enhance both cerebrovascular and cognitive function may be particularly important for persons living with SCI to reduce the risk for secondary complications (such as cerebrovascular disease) and the development of cognitive impairment. The results of our study demonstrate those with SCI have reduced NVC as compared to AB. This may be due to impaired sympathetic cerebrovascular control as well as low resting systemic blood pressure. As the PCA is directly related to effective perfusion of the medullary autonomic centres in the brain, our study may highlight an important connection between impaired cerebral perfusion of the brainstem and autonomic dysfunction after SCI (


ACE2 gene maps to a quantitative trait locus on the X chromosome in three strains of genetically hypertensive rats, suggesting that ACE2 may be a candidate gene for hypertension. It is hypothesized that disruption of tissue ACE/ACE2 balance results in changes in blood pressure, with increased ACE2 expression protecting against increased blood pressure, and ACE2 deficiency contributing to hypertension. Experimental hypertension studies have measured ACE2 in either the heart or kidney and/or plasma, and have reported that deletion or inhibition of ACE2 leads to hypertension, whilst enhancing ACE2 protects against the development of hypertension, hence increasing ACE2 may be a therapeutic option for the management of high blood pressure in man. There have been relatively few studies of ACE2, either at the gene or the circulating level in patients with hypertension. Plasma ACE2 activity is low in healthy subjects, but elevated in patients with cardiovascular risk factors or cardiovascular disease. Genetic studies have investigated ACE2 gene polymorphisms with either hypertension or blood pressure, and have produced largely inconsistent findings. This review discusses the evidence regarding ACE2 in experimental hypertension models and the association between circulating ACE2 activity and ACE2 polymorphisms with blood pressure and arterial hypertension in man.Hypertension is a major risk factor for stroke, coronary events, heart and renal failure, and the renin-angiotensin system (RAS) plays a major role in its pathogenesis. Within the RAS, angiotensin converting enzyme (ACE) converts angiotensin (Ang) I into the vasoconstrictor Ang II. An “alternate” arm of the RAS now exists in which ACE2 counterbalances the effects of the classic RAS through degradation of Ang II, and generation of the vasodilator Ang 1-7. ACE2 is highly expressed in the heart, blood vessels, and kidney. The catalytically active ectodomain of ACE2 undergoes shedding, resulting in ACE2 in the circulation. The  Ang II has actions to raise blood pressure through vasoconstriction and salt and water retention  may counteract AT1R mediated effects either directly or by modulating AT1R signaling  is the leading cause of death and disability worldwide   rats did not change kidney ACE2 expression and activity -salt, Ang II infusion], renal failure , and renal artery stenosis (Goldblatt hypertension).In DOCA-salt hypertension in the rat, plasma ACE2 activity  hypertensive SD rat model with kidney impairment, kidney ACE2 gene and protein expression were reduced in both clipped and non-clipped kidneys   treatment partially reduced the pressor effect of an Ang II infusion without affecting basal systolic blood pressure in vehicle-treated mice , serum ACE2 activity was significantly higher in male compared to female patients, and was positively correlated with systolic blood pressure in both males and females , hemodialysis patients (n = 100) and kidney transplant recipients (n = 80)  compared to healthy individuals (n = 45).A number of other studies suggest an association between ACE2 activity and blood pressure. In patients with type 1 diabetes (n = 95), there was no association between ACE2 activity and hypertension  with blood pressure and/or hypertension  or normotension (n = 193), four ACE2 SNPs were not associated with hypertension  were investigated but none were associated with systolic blood pressure variation  were reported to be significantly associated with the diastolic blood pressure response to a cold pressor test in female Chinese subjects participating in the GenSalt study (Huang et al., ACE2 SNPs rs2106809 and rs2285666 with orthostatic blood pressure dysregulation in 3630 untreated hypertensive patients compared to 826 normotensive subjects (Fan et al., In another analysis, three ACE2 SNPs with baseline blood pressure and blood pressure changes over 5 years was examined in 555 adolescents mainly of French Canadian or European descent (Malard et al., ACE2 SNP rs2074192 minor A allele was associated with a lower baseline diastolic and systolic blood pressure after weight and height adjustment. The ACE2 SNP rs233575 C allele was associated with higher baseline systolic and diastolic blood pressure in European males. In contrast, French Canadian females with the rs233575 T allele had a 4 mmHg higher baseline diastolic blood pressure compared to the SNPs C allele. With regards to ACE2 SNPs associated with changes in blood pressure from the baseline visit, there were no significant associations with the four ACE2 SNPs investigated in European or French Canadian males. However in females of European descent, the rs2074192 A allele was associated with a change in systolic blood pressure that was lower and the C allele of SNPs rs2333575 and rs2158083 were associated with a change in systolic blood pressure that was higher compared to the alternative allele (Malard et al., ACE2 SNPs with blood pressure was influenced by both gender and ethnicity.The association of ACE2 polymorphisms. The GenSalt study in Chinese Han subjects examined responses to variation in sodium and potassium intake (Zhao et al., ACE2 SNPs to be associated with the reduction in blood pressure in response to potassium while on a high salt intake in males only (Zhao et al., ACE2 gene associations with blood pressure treatment responses in Caucasian populations.A small number of dietary and pharmacological interventions in Chinese populations have also been conducted in relation to The experimental studies clearly support a physiological and pathophysiological role for ACE2 in arterial hypertension, and data is also available that increasing/activating ACE2 has beneficial effects to lower blood pressure. As therapeutic strategies that block the RAS using ACE inhibitors or Ang II receptor blockers are first line therapy in hypertension, experimental studies are needed that combine ACE2 activators/recombinant ACE2 with RAS blockers to determine if this approach offers incremental benefits.ACE2 genetic associations with blood pressure and hypertension; the majority are in Chinese populations, but the results have been inconsistent. There are not yet any studies that combine genetic approaches with measurement of plasma ACE2 activity. Large carefully conducted clinical studies, designed with sufficient numbers and power to allow separate analyses of males and females are urgently needed in patients with hypertension to more precisely clarify the potential role of ACE2 in blood pressure variation and hypertension, and to uncover mechanisms that might offer novel treatment targets.There are very few clinical studies that have specifically investigated whether circulating ACE2 activity is associated with blood pressure or hypertension. Plasma ACE2 activity levels are low in healthy individuals, and may or may not be increased in patients with hypertension. Males have higher circulating ACE2 activity than females, but few reports have analyzed data according to gender. There are 17 studies that have examined The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


We used contrast-enhanced ultrasound (CEUS) to estimate the effect of an increase in mean arterial pressure (MAP) induced by noradrenaline infusion on renal microvascular cortical perfusion in critically ill patients.Twelve patients requiring a noradrenaline infusion to maintain a MAP more than 60 mmHg within 48 hours of intensive care unit admission were included in the study. Renal CEUS scans with destruction-replenishment sequences and Sonovue®  as a contrast agent, were performed at baseline (MAP 60 to 65 mmHg) and after a noradrenaline-induced increase in MAP to 80 to 85 mmHg.There was no adverse effect associated with ultrasound contrast agent administration or increase in noradrenaline infusion rate. Adequate images were obtained in all patients at all study times. To reach the higher MAP target, median noradrenaline infusion rate was increased from 10 to 14 μg/min.P = 0.38). At individual level, however, we observed important heterogeneity in responses (range -51% to +97% changes from baseline).Noradrenaline-induced increases in MAP were not associated with a significant change in overall CEUS derived mean perfusion indices (median perfusion index 3056 (interquartile range: 2438 to 6771) arbitrary units (a.u.) at baseline versus 4101 (3067 to 5981) a.u. after MAP increase, A noradrenaline-induced increase in MAP was not associated with an overall increase in renal cortical perfusion as estimated by CEUS. However, at individual level, such response was heterogeneous and unpredictable suggesting great variability in pressure responsiveness within a cohort with a similar clinical phenotype.The online version of this article (doi:10.1186/s13054-014-0653-3) contains supplementary material, which is available to authorized users. Renal blood flow (RBF) and glomerular filtration rate (GFR) are normally autoregulated when systemic mean arterial pressure (MAP) is maintained between 60 and 100 mmHg ,3 to be Based on this knowledge, intensive care physicians often aim at maintaining a higher MAP in patients deemed at risk of AKI and in those with chronic hypertension . An arbiHowever, such an increase in the MAP target means higher exposure to a drug with recognized dose-dependent side effects . To dateContrast-enhanced ultrasonography (CEUS) is a novel imaging technique that uses low mechanical-index ultrasonography and microbubble-based contrast agents. CEUS has been shown to be able to detect changes in microvascular RBF -17. CEUSWe have designed a pilot observational study using CEUS to determine changes in renal cortical microvascular blood flow associated with noradrenaline-induced increases in MAP from 60 to 65 mmHg to 80 to 85 mmHg in critically ill patients and related these changes to clinical outcomes.The study was approved by the Austin Health Research Ethics Committee (H2012/04592).in situ, required a noradrenaline infusion >5 μg/minute and expected to require noradrenaline for >24 hours at the time of inclusion, were approached and consented within 48 hours of ICU admission (consent could be obtained from the patient or next of kin). Exclusion criteria were: Sonovue® or any ultrasound contrast agent (UCA) intolerance, intra-cranial hypertension, aortic dissection or aneurysm, decompensated heart failure, severe left ventricular dysfunction (left ventricular ejection fraction <30%), ischaemic heart disease, ventricular arrhythmia, end-stage renal disease , ongoing renal replacement therapy (RRT), inability to obtain informed consent, concern of the treating physician that a MAP of 60 mmHg might be too low or a MAP of 80 mmHg might be too high, and enrolment in a conflicting research study.Twelve patients who had an arterial line After obtaining written consent, renal CEUS scans were performed (procedure detailed below). The first scan was performed at baseline with the commonly applied MAP level of 60 to 65 mmHg. The noradrenaline infusion was then titrated up to reach a MAP of 80 to 85 mmHg. After a 30-minute equilibration period, the CEUS scan was repeated. The rate of the noradrenaline infusion was then titrated back to the original MAP target as per treating physician recommendations.All studies were performed within the ICU. Patients received full monitoring according to their clinical stability at the time of the examination as evaluated by the treating physician. At a minimum, invasive blood pressure, blood oxygen saturation (via pulse oxymetry), and continuous three-lead electrocardiograms were available in all patients throughout the experiment. In addition, urinary output was monitored on an hourly basis and blood samples regularly drawn for routine blood tests as per clinical practice.For the purpose of this study, we used Sonovue®  as an ultrasound contrast agent (UCA). The UCA was infused into a peripheral or central vein (according to availability) through an intravenous cannula using a dedicated syringe pump. Low mechanical index ultrasound of the kidney was performed with a Philips IU22® ultrasound machine and a C5-1® 5 MHz probe. A long-axis view of the kidney was obtained by placing the transducer probe over the lower back of the subject. Once adequate images of the kidney were obtained, UCA infusion was started at 1 ml/minute. Image depth, focus, gain and frame rate were optimized at the beginning of each experiment and held constant during the study. After a 2-minute period required to obtain a steady state, five consecutive destruction/refilling sequences (with 15-s refilling time) were obtained . DestrucUltrasound datasets were exported in a digital imaging and communication in medicine (DICOM) format and analysed offline using a dedicated software package, VueBox® . An example of offline analysis is presented in Figure Suboptimal sequences with inadequate insonification or excessive movement artefact were excluded. For each patient and study time, the median value for interpretable measurements was considered for analysis. Given the expected inter-observation variability and based on previous research , a changnot consistent when both parameters increased or decreased by >25% of their baseline value in a direction indicating an opposite change in blood flow. The value of 25% corresponds to the mean coefficient of variation for mTT.As perfusion indices are calculated based on two measured parameters (RBV and mTT), we sought to report the agreement between these two measurements. For the purpose of this analysis, we considered that changes in RBV and changes in mTT were consistent when, in a given patient, both parameters increased or decreased by >25% of their baseline value in a direction indicating similar change in blood flow , or when one parameter increased or decreased by >25% of its baseline value and the other one was unchanged (<25% change). We considered that changes were Patients were classified into responders if their PI increased by >25% after noradrenaline-induced increase in MAP compared with baseline. They were classified into non responders if PI increased by <25% or decreased after a noradrenaline-induced increase in MAP.t-test. Non-normally distributed data are presented as median (interquartile range) and were compared using Wilcoxon matched-pairs signed-rank test. A two-sided P-value of 0.05 was considered to be statistically significant.Analyses were performed using SPSS® version 21 . All outcomes were assessed for normality and as RBV, mTT and PI were all well-approximated by log-normal distributions, each was log-transformed prior to analysis. Precision of measurements was estimated by calculating the coefficient of variation, defined as SD divided by the mean value and multiplied by 100 for all sequences obtained at one study time. We report the mean average coefficient of variation for the three CEUS-derived parameters. Normally distributed data are reported as mean (SD) and compared using the paired Patients; demographics and outcomes are detailed in Table Ten patients developed AKI during their hospital stay according to the RIFLE classification  but noneOverall, 24 CEUS scans were performed using a total of 48 vials of Sonovue® (10 ml per scan). No adverse effect was noted with UCA administration. At least one interpretable sequence was obtained for each patient at the two study times. Each CEUS examination took approximately 15 minutes to complete. To increase MAP from 60 to 65 mmHg to 80 to 85 Hg, the median noradrenaline infusion rate was increased from 10 μg/minute (interquartile range (IQR) 5.5 to 12.5) to 14 μg/minute (IQR 10.5 to 18.5). No adverse event was associated with the increase in MAP and noradrenaline dose.The mean coefficients of variation were 12.2% for RBV, 25.2% for mTT and 25.2% for PI.P = 0.38.Overall Figure , there wHowever, at the individual level Figure  large vaAmong the three patients with chronic hypertension, noradrenaline-induced MAP increase was associated with 10% and 93% increase in two patients, but 50% decrease in the remaining patient.Patient-level changes from baseline for RBV and mTT are presented in Figure Four patients  in which ventilation parameters, fluid and medications infusions, patient-position and US machine settings were all kept constant. Only comparison of measurements obtained in a single patient, as all other factors are kept constant can be interpreted. CEUS data were obtained by a single experienced operator aware of all these limitations.In ventilated patients with low tidal volumes, respiration-related renal displacement can be dealt with by selecting a probe angle limiting this motion and by the use of an advanced image stabilisation algorithm in the VueBox® software. Therefore, a breath-holding manoeuvre was not necessary.Consistency between parameters used to determine perfusion indices was fairly good, however, 25% of measurements suggested changes in perfusion in opposite directions. Further studies would be required to clarify the causes of such disagreements, how to prevent them and how to handle them.Finally, the clinical relevance of our findings and the applicability of CEUS derived parameters remains to be determined. Indeed, as illustrated by a recent animal study  the relaAn increase in MAP as induced by noradrenaline infusion was not associated with overall changes in renal microvascular cortical perfusion as evaluated by CEUS. However, some individual patients seem to have marked responses (either increase or decrease). Further studies are required to establish whether such patients would benefit from tailored MAP targets.A noradrenaline-induced increase in MAP is not associated with an overall increase in renal cortical perfusion as estimated by CEUSHowever, at individual level, such response was heterogeneous and unpredictable, suggesting great variability in pressure responsiveness within a cohort with a similar clinical phenotype


Background: Sleep apnea is accompanied by some cardiovascular complications. It has even been hypothesized that sleep apnea, itself, can induce some of these complications. Given such controversies, we assessed the left ventricular mass index (LVMI) and systolic pulmonary artery pressure in patients with sleep apnea.Methods: Through convenience sampling, 56 patients with the obstructive sleep apnea syndrome (OSAS) were included in the present descriptive cross-sectional study. Patients with any past history of hypertension and diabetes mellitus were excluded. The apnea severity was assessed via the polysomnography-derived apnea-hypopnea index (AHI). All the patients underwent transthoracic echocardiography. In this cross-sectional study - data regarding age, gender, smoking, systolic and diastolic blood pressures, polysomnographic parameters , and echocardiographic parameters (systolic pulmonary artery pressure and LVMI) were accumulated and processed.Results: Fifty-two men and 14 women at a mean age of 49.29 ± 11.79 years participated in this study. Systolic and was significantly high in the severe group compared with the mild group . The LVMI was increased parallel to an increase in the severity of the OSAS, but that increase was not statistically significant . The d.SaO2 < 90% was positively correlated with the LVMI, and this relationship remained true after adjustment for the body mass index .Conclusion: Severe OSAS was accompanied by a higher blood pressure. The LVMI did not differ significantly between the patients with the OSAS and those who did not suffer from other risk factors of cardiac diseases. Hypoxia and ventilatory efforts are the consequences of this condition, and transient arousal occurs to improve the air flow. An obstructive apnea is the absence of the air flow accompanied by ventilatory efforts for at least 10 seconds. A hypopnea is considered clinically significant if it is associated with a central nervous system arousal or with an oxyhemoglobin desaturation event (a decrease in blood oxygen saturation [SaO2] by 3 to 4% or more).1 The apnea-hypopnea index (AHI) is the total number of apneas and hypopneas per hour of sleep. The AHI is a common and useful index for evaluating the severity of the OSAS. Patients are classified into three groups based on their AHI: mild , moderate , and severe (AHI ≥ 30).1 Several causes have been mentioned to explain how the cardiovascular complications are related to the OSAS- including increased sympathetic activity in response to hypoxia and hypercapnia, which itself causes vasoconstriction, acute tachycardia, acute blood pressure elevation, and decrease in cardiovascular variability.2, 3 The OSAS is prevalent in patients with cardiovascular disease. It has been estimated that 50% of patients with hypertension, 33% with coronary artery disease, 50 to 60% with myocardial infarction, 30 to 40% with systolic heart failure, and 50% with atrial fibrillation requiring cardioversion suffer from the OSAS.2 On the other hand, some cardiovascular complications are presumed to be the consequences of the OSAS. This relationship may be caused by the OSAS comorbidities such as obesity and metabolic dysregulations. However, according to observational studies, the OSAS - itself - may lead to or worsen cardiovascular complications.Sleep-disordered breathing includes the obstructive sleep apnea syndrome (OSAS) and the upper airway resistance syndrome. Epidemiological studies based on the general population or the community-based cohort between 30 and 60 years of age estimate that 2 to 5% of the population is affected by the OSAS.2, lowest SaO2, and duration of SaO2 (d.SaO2) < 90%, and echocardiographic parameters (systolic pulmonary artery pressure and left ventricular mass index [LVMI]). The (LVMI) was calculated according to the Devereux formula. The LVMI was calculated by the correction of the left ventricular mass (LVM) for the body surface area. The normal threshold for the LVMI was defined < 96 for women and < 116 for men.4 The patients were divided into three groups according to their AHI: mild , moderate , and severe (AHI ≥ 30). For the statistical analyses, the statistical software SPSS version 13 for Windows  was used. The quantitative variables were presented as means ± standard deviations for the normally distributed variables and as medians (interquartile ranges) for the variables without normal distribution. The categorical data were presented as numbers and percentages. The categorical data were compared using the chi-square test, whereas the quantitative ones were compared using the one-way analysis of variance and the Kruskal–Wallis test, as appropriate. Relationships were assessed using the Pearson correlation test, Spearman test, or Kendall test based on their distribution. All p values were two-tailed, and a p value < 0.05 was considered statistically significant.Fifty-eight patients diagnosed with the OSAS via polysomnography were enrolled in this cross-sectional study, conducted from March 2011 to May 2013. Unfortunately, recruiting only a small population with sleep disorders having undergone polysomnography and accepted to undergo echocardiography was one of the major limitations to our study. The patients underwent polysomnography in Nour Sleep Disorders Clinic, followed by echocardiography in Rasoul-e-Akram Hospital, Tehran, Iran. The study was performed in accordance with the Declaration of Helsinki and subsequent revisions. Furthermore, the Ethics Committee of Iran University of Medical Sciences approved the protocol before the study was commenced. Two patients were excluded from the study because of the diagnosis of severe mitral stenosis and myopathy due to frequent premature ventricular contractions on echocardiography. Patients with hypertension, diabetes mellitus, chronic kidney disease, cardiomyopathy, and any past history of cardiopulmonary diseases as well as individuals with the AHI < 5 assumed as the normal population1 were excluded from the study. Transthoracic echocardiography was performed by a single fellow of echocardiography. The echocardiographer was blinded to the patients' polysomnography report. A manual check list was devised for data collection. The data encompassed age, gender, smoking, systolic and diastolic blood pressures, polysomnographic parameters . Thirteen (23.2%) patients had mild OSAS with a mean AHI of 7.23 ± 1.61 (Group I). Fifteen (26.8%) patients were in the moderate group (Group II)  and 28 (50%) were in the severe group (Group III) . The demographic data and echocardiographic parameters were compared between the groups. The 56 eligible patients recruited in this study were comprised of 42 (75%) men and 14 (25%) women. The mean age was 49.29±11.79 years old, and the mean body mass index (BMI) was 28.12 ± 3.59 kg/m2) and Group III (29.25 ± 4.06 kg/m2), . A partial correlation was used with controlling for the body mass index (BMI). There were no significant differences between the groups regarding systolic pulmonary artery pressure . The LVMI was increased parallel to an increase in the OSAS severity, but that increase failed to constitute statistical significance  (Table 2). Six patients were diagnosed with LV hypertrophy; 4 (66.6%) of these patients were in Group III. Significant correlations were detected between the BMI and each of the hypoxic parameters - including the AHI, mean SaO2, lowest SaO2, and d.SaO2 < 90% . Similarly, a significant positive correlation was detected between the BMI and systolic blood pressure . Although the initial analysis showed a negative correlation between systolic blood pressure and mean SaO2 , a negative correlation between systolic blood pressure and lowest SaO2 , and a positive correlation between systolic blood pressure and d.SaO2 < 90% , these relationships were not confirmed after adjustment for the BMI. The LVMI was positively correlated with d.SaO2 < 90%, even after adjustment for the BMI . There were no statistically significant correlations between the LVMI and the other hypoxemic parameters - including the AHI (r = 0.32), mean SaO2 (r = -0.24), and lowest SaO2 (r = -0.19).No significant differences were detectable between the groups concerning age , whereas systolic blood pressure was significantly high in the severe group compared with the mild group . Additionally, a lower diastolic blood pressure was demonstrated in the mild group than in both the moderate and severe groups  (Table 2). The BMI differed significantly between Group I  and Group III (29.25 ± 4.06 kg/m2), and there were significant correlations between the BMI and each of the hypoxemic parameters - including the AHI, mean SaO2, lowest SaO2, and d.SaO2 < 90%.7 Our results also revealed no significant differences between the groups apropos pulmonary artery pressure. The LVMI was increased in tandem with a rise in the OSAS severity in our study; the increase, however, was not statistically significant. The LVMI was positively correlated with the d.SaO2 < 90%, even after adjustment for the BMI. This relationship was not true between the LVMI and the other hypoxemic parameters - including the AHI, mean SaO2, and lowest SaO2. In our study, 6 patients had LV hypertrophy; 4 (66.6%) of these patients were in the severe apnea group. It has been previously reported that the OSAS is an independent predictor for the occurrence of LV hypertrophy.8 Nonetheless, a study performed between 1990 and 1998 on patients with the OSAS demonstrated that the LV hypertrophy in these patients was associated with higher age, obesity, and hypertension.9 Dursunoglu et al10 reported that the LVMI in patients with the AHI ≥ 15 was higher than that in individuals with the AHI < 15. Another study on 28 patients with the OSAS without any past history of cardiovascular diseases showed LV hypertrophy in 21%; nevertheless, the effect of age and the BMI were not taken into consideration in this study  patients before clinical manifestation, Hall 2009,15:3686). It has been believed that LV hypertrophy in patients with the OSAS was independent of the other risk factors and that there was a relationship between this complication and O2 desaturation  and diastolic dysfunction (DD) in obstructive sleep apnea (SAHS) patients. Hall 2009, 15:3698.). In another study on 50 patients with the OSAS, all the patients who were diagnosed with LV hypertrophy suffered from hypertension and the LVMI was strongly associated with the d.SaO2 < 90%.11 According to another study, the relationship between the severity of the OSAS and LV thickness was weakened by an increase in age and smoking and was invigorated by hypertension.12Fifty-six patients with the OSAS participated in our cross-sectional study and underwent transthoracic echocardiography. The initial analysis showed correlations between systolic blood pressure and hypoxemic parameters, but these relationships were not confirmed after adjustment for the BMI in our study. A 4-year study on 709 subjects demonstrated that the OSAS was a risk factor for elevating blood pressure after adjustment for age, gender, neck circumference, and the BMI.2 < 90%.Severe OSAS is accompanied by a higher blood pressure. Whereas the LVMI did not differ significantly between the patients with the OSAS who were not heavy smokers and did not suffer from hypertension and/or diabetes mellitus, LV hypertrophy occurred more frequently in those with severe OSAS (66%) than in those who belonged to the mild and moderate groups. Finally, an increase in the LVMI was correlated with a rise in the d.SaO


Chronic kidney disease (CKD) is a worldwide health problem. However, despite to new routes of dialysis, mortality and morbidity is high. One of the most common symptom of CKD is anemia, especially is more obvious in stages 3 and 4. In this review, we compared the effects of erythropoietin and anemia correction on kidney function (GFR) by investigating in various studies. Despite extensive studies in this category, still we do not sure about the effects of erythropoietin and anemia correction on the glomerular filtration rate. It seems that the treatment of anemia by recombinant human erythropoietin in chronic kidney disease, when it accompanied by control of metabolic complications, can improve anemia, however more human studies needs to find the effect of erythropoietin on kidney function.Chronic kidney disease (CKD) is a serious problem in the general population. There is a growing trend in prevalence and incidence of renal failure in the United States . In thisIn the absence of erythropoietin, precursor cells of red blood cells in bone marrow are destroyed (apoptosis). By loss of tissues, around the kidney tubules and its failure, amount of erythropoietin production reduced and anemia occurs . In seveet al. was evaluated the relationship of serum erythropoietin (EPO) levels to hematocrit and glomerular filtration rate (GFR) in patients with CKD. The EPO levels was measured by radioimmunoassay in 119 blood samples from 48 patients obtained over a period of up to 5 years. Hematocrit values correlated significantly with the GFR, but serum EPO levels did not change with a decline in the GFR. Significant anemia was noted only when the GFR fell below 20 ml/min/1.73 m2. The results of this study suggest that the tissue oxygenation-EPO-hematocrit feedback mechanism operates at a lower set point in patients with CKD in comparison with normal subjects . They found a significant correlation between the increase in total hemoglobin and the increase in exercise capacity in the EPO-treated group  and also in four three-month period included three-month period before intervention, time of intervention, the first and second quarter after intervention were not statistically significant . Indeed subjects . Anemia  indices . The wei indices . Ble et n levels . Howevern levels ,16.A European clinical trial demonstrated that erythropoietin therapy resulted in a greater reduction in exposure to allogeneic blood during orthopedic surgery in patients who donated autologous blood and were anemic  than in placebo-treated patients . HoweverIt seems that the treatment of anemia by recombinant human erythropoietin in chronic kidney disease, when it accompanied by control of metabolic complications, can improve anemia but has not any effect on reduction of renal function rate. For confirming of erythropoietin effect on renal function, we need a study with larger samples size and longer period of time.We thank Mr Mehrdad Zahmatkesh for helping in writing this article.Main draft write up and editing by MRT. Important intellectual content and critical revision by SSBM.The author declared no competing interests.Ethical issues  have been completely observed by the authors.None declared.


Biphasic cuirass ventilation (BCV) is a form of non-invasive extrathoracic positive and negative pressure mechanical ventilation. The present study was conducted to quantify our positive experience using BCV to dramatically improve gas exchange and cardiac function in patients with acute exacerbation of chronic respiratory failure and secondary pulmonary hypertension (PH).2) was measured before and after each daily BCV session, and right heart catheter test  and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before and after a series of BCV sessions.BCV was applied for 2 weeks in 17 patients with PH caused by lung disease. Ventilation sessions were limited to 1 h per day to prevent exhaustion. To assess respiratory and circulatory effects, percutaneous arterial oxygen saturation . PAOP, CI and serum NT-proBNP levels decreased compared with baseline. No patients were treated with epoprostenol, iloprost, bosentan or sildenafil for PH.SpOBCV may improve circulatory function in patients with PH caused by lung disease.The online version of this article (doi:10.1007/s00540-016-2172-7) contains supplementary material, which is available to authorized users. Structural and functional alterations of pulmonary vessels eventually lead to secondary pulmonary hypertension (PH) and cor pulmonale  in patieBiphasic cuirass ventilation (BCV), a form of non-invasive extrathoracic mechanical ventilation, is an advanced model of the iron lung. It consists of a cuirass and a pressure source capable of providing both positive and negative pressure, which supports spontaneous breathing in a more physiological manner compared with positive pressure ventilation. BCV remains in clinical use and has been shown to be as effective as non-invasive positive pressure ventilation for avoiding tracheal intubation in COPD patients .Negative pressure ventilation (NPV) provided by BCV increases pulmonary blood flow after the Fontan operation  and imprThis observational study involved patients recruited from Tokyo Women’s Medical University Hospital and Synthesis Shinkawabashi Hospital in Japan. The study was conducted from April 2009 until April 2012 using a protocol approved by the ethics committee from each hospital. Written informed consent was obtained from all patients.PH was defined as mean pulmonary artery pressure (mPAP) >20 mmHg in accordance with guidelines from the Japanese Cardiac Society (2006). Steady-state PAP was measured by right heart catheterization. Exclusion criteria were (1) PH caused by idiopathic pulmonary arterial hypertension, connective tissue disease, chronic thromboembolism, portal hypertension, congenital heart disease, left heart disease, chronic hemolytic anemia, HIV infection or other unknown reason; (2) acute exacerbation of chronic lung disease; (3) unstable hemodynamics ; (4) infection of any organ; (5) pulmonary vasodilator medication, such as epoprostenol, iloprost, bosentan, or sildenafil; (6) failure in cuirass attachment due to a skin problem; and (7) otherwise judged by a physician as inappropriate for study inclusion.Patients who regularly visited the hospital with dyspnea secondary to chronic lung disease were diagnosed with PH using ultrasonic echocardiography. First, right heart catheterization was performed and PH was definitively diagnosed during an approximate 2-week admission. Hemodynamics were measured at the same time (prior to starting a series of BCV sessions). BCV was performed on consecutive weekdays and a second right-heart catheterization was performed just before hospital discharge to compare hemodynamics before and after BCV. Patient chest X-ray, blood analysis and pulmonary function tests were rechecked for comparison with results from the day of admission.2) were continuously monitored. Noninvasive blood pressure was recorded every 5 min and arterial blood gas was analyzed. Central venous pressure, right atrial pressure (RAP), PAP, pulmonary artery occlusion pressure (PAOP) and cardiac index (CI) were measured using a thermodilution catheter with jugular venous access. mPAP and PVR were calculated using the formula: mPAP = diastolic PAP + (systolic PAP − diastolic PAP)/3, PVR = (mPAP − PAOP)/cardiac output.Right heart catheterization was performed at the beginning of an approximate 2-week admission. In each test, electrocardiograph and percutaneous arterial oxygen saturation (SpO2O (synchronized to each patient’s inspiration) and a positive pressure from 3−10 cmH2O (synchronized for expiration). BCV sessions were limited to 30–60 min/day to prevent exhaustion. Ventilatory rate and inspiratory:expiratory ratio were set and adjusted to synchronize with spontaneous breathing. To maintain stable conditions and record changes in oxygenation, SpO2 was continuously monitored for several minutes prior to starting and after completing BCV.BCV was performed every weekday during admission using an RTX ventilator . To promote biphasic pressure with a time cycle, the control mode was used as an initial setting with a negative pressure from −15 to −25 cmHVenous blood samples were taken at admission and before discharge. Complete blood count, serum concentrations of N-terminal proB-type natriuretic peptide (NT-proBNP) and noradrenalin were measured for comparison.Pharmacological treatments initiated prior to admission were not interrupted during the course of study. Long-term oxygen therapy was maintained on one patient, with the flow dose of oxygen remaining unchanged. After the BCV study, all patients were asked the following three questions—Was the BCV comfortable? Did the BCV improve your dyspnea? Would you like to use the BCV at an outpatient clinic?t test was employed; whereas, for skewed numerical data, a Wilcoxon rank sum test was applied. SpO2 changes were analyzed using Kruskal–Wallis test. Two-sided P values <0.05 were considered statistically significant.Statistical analysis was performed using JMP software, version 11.2.0 . Normally distributed numerical data are expressed as mean and standard deviation (SD) values, whereas skewed data are expressed as median and interquartile range. Qualitative data are expressed as number and percentage. For normally distributed numerical data, Student’s n = 3), interstitial pneumonia (n = 1) or pulmonary asbestosis (n = 1). The COPD group included individuals at various stages of Global Initiative for Chronic Obstructive Lung Disease .Seventeen patients with steady-state PH caused by chronic lung disease were included in the study; Table Of the 17 patients, 15 underwent catheterization twice and a series of BCV sessions during an approximate 2-week admission. The remaining two patients underwent right heart catheterization first, but were discharged before BCV because of financial reasons or the Great East Japan Earthquake; however, they were readmitted to the hospital for BCV. The number and final timing of BCV sessions administered during an approximate 2-week admission Table a, b vari2 returned to baseline levels by the following day , RAP , PAOP  and CI , whereas PVR was unchanged .BCV improved oxygenation after each session; however, this effect was transient and SpOday Fig. a–c. FurtP = 0.0056, Fig. P = 0.599]. Mean blood pressure decreased significantly after each BCV session (Table A significant decrease was observed in serum NT-proBNP levels [136.5 (23.5–357.4) to 60.2 (39.4–190) pg/ml, P = 0.0167; restriction, P = 0.0481; Table P = 0.003), PAOP . Improvement of thoracic mobility increases ventilation volumes and allows for comfortable respiration in restrictive lung disease patients. Indeed, all restriction group patients requested further BCV therapy after discharge. Extra-thoracic positive pressure during expiration assisted return to resting position and may assist in elastic recoil of the chest wall (see Online Resource 1).Pressure swings caused by airflow limitation and reduction of the vascular bed have been shown to elevate PAP in COPD patients , 20. SevSecond, BCV may decrease the work required for breathing by influencing interactions between respiration and circulation. CI decreased statistically, but data recovered to normal ranges. BCV may decrease cardiac load to reduce excess work of breathing associated with chronic lung disease and decreased serum NT-proBNP. It is highly likely that mitigation of breathing workload normalizes CI. Furthermore, improvement in thoracic mobility by BCV, both inspiratory and expiratory support, correlates with decreased work of breathing.We anticipated PVR would decrease during this study, but results from our series of BCV sessions indicated unchanged PVR in all cases and subgroup analyses. Whole parameters, including CI, significantly decreased in the right cardiopulmonary unit, i.e., data recovered to within normal ranges. In our study, BCV may reduce exercise load by positively impacting inefficient respiration within patients.BCV is one type of NPV approach; positive pressure ventilation does not have a similar effect on pulmonary circulation. Negative pressure ventilators using a whole body-sized box are still used in Europe, but this type utilizes continuous external negative pressure regardless of inspiratory and expiratory phases of the respiratory cycle. In contrast, BCV used in our study affects only the thorax and supports both inspiration and expiration individually. Thus, its effects are different from those exerted by continuous NPV. We believe that the effects displayed in this study are unique to BCV.NT-proBNP plays a pivotal role in predicting PH—a reduction of >15 % per year is associated with improved mortality , 27. As Other limitations of the current study include the small sample size, especially for the restriction group. Furthermore, this study was not designed as a control trial because of various limitations in controlling patient conditions. Ethical problems would have arisen if the control group had right heart catheterization performed twice during the study period without therapeutic intervention with BCV. Finally, as catheterization procedures within each facility could only be scheduled on certain days of the week, BCV sessions frequently had to be rescheduled. In general, BCV sessions were performed on weekdays because of insufficient availability of human resources at weekends. As implementation of BCV was negatively affected by weekends, holidays and unexpected human resource problems, the number and timing of BCV sessions consequently varied.It is possible that resting in hospital without any workload is associated with the observed reduction of patient blood pressures. However, it is unlikely that bed rest for approximately 2 weeks solely underlies the significant decreases observed in mPAP, RAP, PAOP, CI, mean BP and NT-proBNP in patients presenting with chronic respiratory disease for decades. Furthermore, none of the patients had worked for several years, remaining at home most days because of respiratory failure.A series of BCV sessions significantly decreased mPAP in this patient cohort. As improvement in oxygenation by BCV was transient, other factors—especially decreased cardiac overload—likely play a role. BCV may provide a promising approach for treating PH caused by chronic lung disease. However, additional studies are needed to define duration, frequency and long-term effects of BCV in a larger sample size. Further consideration of the influence of BCV on respiration and circulation is required, as well as determination of mechanisms underlying potential patient benefits.Supplementary material 1 (PDF 66 kb)Supplementary material 2 (MPG 1210 kb)Supplementary material 3 (MPG 2610 kb)Below is the link to the electronic supplementary material.


Obesity, a well-known risk factor for developing cardiovascular disease (CVD), is associated with chronic periodontitis in adults. This cross-sectional pilot study on obese adolescents was designed to investigate whether periodontal disease in terms of pathological periodontal pockets is associated with raised blood pressure and other risk markers for CVD.The study included 75 obese subjects between 12 to 18 years of age, mean 14.5. Subjects answered a questionnaire regarding health, oral hygiene habits and sociodemographic factors. A clinical examination included Visible Plaque Index (VPI %), Gingival inflammation (BOP %) and the occurrence of pathological pockets exceeding 4 mm (PD ≥ 4 mm). Blood serum were collected and analyzed. The systolic and diastolic blood pressures were registered.Adolescents with pathological periodontal pockets  had significantly higher BOP >25% (P = 0.002), higher diastolic blood pressure (P = 0.008), higher levels of Interleukin (IL)-6 (P < 0.001), Leptin (P = 0.018), Macrophage Chemoattractant Protein-1 (MCP-1) (P = 0.049) and thyroid stimulating hormone (TSH) (P = 0.004) in blood serum compared with subjects without pathological periodontal pockets . The bivariate linear regression analysis demonstrated that PD ≥ 4 mm (P = 0.008) and systolic blood pressure (P < 0.001) were significantly associated with the dependent variable “diastolic blood pressure”. The association between PD ≥ 4 mm and diastolic blood pressure remained significant (P = 0.006) even after adjusting for potential confounders BMI-sds, age, gender, mother’s country of birth, BOP >25%, IL-6, IL-8, Leptin, MCP-1, TSH and total cholesterol in the multiple regression analysis.In conclusion, this study indicates an association between pathological periodontal pockets and diastolic blood pressure in obese adolescents. The association was unaffected by other risk markers for cardiovascular events or periodontal disease. The results call for collaboration between pediatric dentists and medical physicians in preventing obesity development and its associated disorders. Obesity, a well-known risk factor for developing cardiovascular disease (CVD), is associated with chronic periodontitis in adults and adolescents -4. The m2) as well as by BMI adjusted for age and gender (BMI-sds) [The present cross-sectional pilot study included 84 obese subjects who were recently referred to the National Childhood Obesity Center, Karolinska University Hospital, Huddinge, from their primary care giver or school nurse. Subjects were consecutively referred to the Division of Pediatric Dentistry, Karolinska Institutet for oral examination as part of the medical investigation at the National Childhood Obesity Center. Approximately one subject per week underwent the registration procedure and this study was conducted during an 18 month period during 2006 and 2007. All subjects lived within the hospitals catchment area and traveled less than one hour to get to the Center. Body weight (kg) and height (m) were determined and obesity was expressed as Body Mass Index (BMI) (kg/mBMI-sds) . The folWe certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during the research. The Ethics Committee at Karolinska University Hospital Huddinge approved the study and all subjects and parents gave consent before participating. All subjects co-operated satisfactorily during examinations, measurement and sample-taking situations.All adolescents answered a questionnaire that covered topics of their medical condition, medication, meal frequency, oral hygiene habits, smoking habits, as well as their parents’ education and country of birth. Parents’ country of birth was categorized into “born in Sweden” or “born abroad”. The educational level of the parents was stratified according to the years of schooling as either ≤ 12 or > 12 years. Participants under 18 years were assisted by a parent when answering the questionnaire.Dental plaque on tooth surfaces was recorded when clearly visible and expressed using the Visible Plaque Index (VPI) . GingivaPocket depth (mm) was recorded by using a graded periodontal probe  and measured to the nearest mm. The occurrence of pathological periodontal pockets was classified when the subject exhibited one or more sites with a pocket depth of ≥ 4 mm. Erupting and deciduous teeth were excluded.Supragingival calculus was recorded on all teeth as present when clearly visible. Subgingival calculus was recorded on the radiographs taken as well as clinically after probing the gingival sulcus. The oral clinical recording was performed by one of the authors (CZ).Systolic and diastolic blood pressure was measured in the sitting position with a mercury sphygmomanometer with a standard pressure cuff of the correct size on the left arm. Blood pressures were measured in duplicates. A third measurement was taken if the two readings differed more than 5 mm Hg and the mean of the two closest readings was used. The same experienced nurse practitioner performed all measurements.Blood samples were taken after an overnight fast starting at midnight. Fasting was confirmed by the child and parent before collecting blood. Blood samples for High density lipoprotein (HDL) were analyzed immediately. Remaining samples were kept frozen in-80°C until analyzed. HDL, TSH and CRP-sensitivity analyzes were performed at a certified laboratory . IL-1β, IL-6, IL-8, MCP-1 and Leptin were analyzed using commercially available Luminex kits . TNF-α levels were measured using Bio-Plex cytokine assay .For analyzing the data, frequency tables, cross tables, ONEWAY ANOVA, Chi-square, linear regression were used by SPSS version 21.0 . Bivariate analyses were carried out between the dependent variable diastolic blood pressure or systolic blood pressure and the independent variables by applying a linear regression model. In the multiple linear regression analysis with diastolic blood pressure as dependent variable, the independent variable PD ≥ 4 mm was adjusted for potential confounders .Confidence Interval 95% was calculated. Level of significance was accepted at P-values less than 0.05. In case of biochemical variables, the Bonferroni test adjusted for intra correlations between the biomedical variables and a P-value of <0.01 was required to declare significance to avoid chance of mass significance.Of the subjects included in this study (n = 75), 14 displayed pathological periodontal pockets (PD ≥ 4 mm) and 61 were without pathological periodontal pockets . There was no significant difference between adolescents with and without PD ≥ 4 mm in regards to age, gender, BMI-sds, tooth brushing habits, sociodemographic factors, medical history or visible plaque index VPI > 25%)  and systolic blood pressure (P < 0.001) Table . As demoIn a bivariate linear regression analysis with systolic blood pressure as dependent variable, diastolic blood pressure (P > 0.001) as well as serum level of TSH (P = 0.039) showed significant association (data not shown).The main finding in this study demonstrates an association between periodontal disease in terms of pathological periodontal pockets and diastolic blood pressure in obese adolescents. Obese subjects with pathological periodontal pockets had significantly higher diastolic blood pressure (74 mmHg) compared with periodontally healthy obese adolescents (67 mmHg). Pediatric subjects with obesity have been reported to have higher systolic and diastolic blood pressure than their normal weight counterparts ,25. The In the current study we used one-time blood pressure measurement in a resting position which is an acceptable screening method . HoweverThe endpoint of inflammatory periodontal disease includes alveolar bone resorption and subsequently loss of teeth. Subjects in this study are young and the effect of chronic inflammation on periodontal tissue needs longer exposure time until alveolar bone loss is possible to detect on the radiographs. Therefore, we used pathological periodontal pocket PD ≥ 4 mm), a variable, commonly used as a periodontal risk indicator in young subjects  in the s mm, a vaTSH has not previously been connected to periodontal disease, but is reported to be enhanced in serum in obese subjects . In thisOur finding that there is an association between PD ≥4 mm and diastolic blood pressure is compatible with the finding in a similar age group that overweight/obese adolescents had significantly higher blood pressure and more gingival inflammation than their normal weight counterparts . HoweverPerpending the finding, that diastolic blood pressure at 18 years of age seems to be a stronger predictor for cardiovascular mortality than systolic blood pressure , it is iThis pilot study has, however, several limitations. Since no normal weight participants are included, the association between periodontal disease and raised diastolic blood pressure might be specific for the obese condition. We did not register the duration of obesity of the subjects which probably also, in addition to the severity of obesity, is of importance when looking at the association between periodontal risk factors and blood pressure. Since this study has a cross sectional design, a longitudinal study is needed before any conclusions can be drawn.This study indicates an association between pathological periodontal pockets and diastolic blood pressure in obese adolescents. The association was unaffected by other risk markers for cardiovascular events or periodontal disease. The results call for collaboration between pediatric dentists and medical physicians in preventing obesity development and its associated disorders.