Neonatal Hip Loading in Developmental Dysplasia: Finite Element Simulation of Proximal Femur Growth and Treatment.

Background: Abnormal prenatal hip joint loading can lead to compromised hip joint function. Early intervention is crucial for favorable outcomes. Purpose: This study investigates the impact of treatment timing (initiation and duration) on cartilage growth and ossification in the proximal femur of infants with developmental dysplasia of the hip, a condition affecting newborns. Methods: We used a mechanobiological model to simulate proximal femur growth during treatment durations of 3 months, 6 months, and a late-start treatment. Results: The findings indicate that the timing of treatment initiation is crucial, while a longer treatment duration does not contribute to improved morphological development of the hip joint. Conclusions: Mechanobiological models of growth can be used to develop treatments and therapies that correct loading conditions. Growing bone is particularly sensitive to loading conditions, and altered loading during growth can affect bone shape and functionality.

Can pelvic tilt cause cam morphology? A computational model of proximal femur development mechanobiology.

Cam deformity of the proximal femur is a risk factor for early osteoarthritis. While cam morphology is related to mechanical force at a formative time in skeletal growth, the specific problematic forces contributing to the development of cam morphology remain unknown. Individuals with femoroacetabular impingement syndrome exhibit an increased anterior pelvic tilt during walking, which alters their hip joint forces. This study aims to investigate the influence of altered joint force caused by anterior pelvic tilt on proximal femur epiphyseal growth and the potential association between increased anterior pelvic tilt and the development of cam morphology. A computational model is utilized to simulate the endochondral ossification in the proximal femur and predict cam formation. Cartilage growth and ossification patterns for a gait cycle with and without anterior pelvic tilt were modeled. The simulated growth results indicated an increased alpha angle (53° for typically developing to 68° for anterior pelvic tilt) and aspherical femoral head in the model with anterior pelvic tilt. We conclude that anterior pelvic tilt may be sufficient to cause the formation of the cam morphology. Identifying the critical mechanical conditions that increase the risk of cam deformity could help prevent this condition by adjusting the physical activities before skeletal maturity.

Computational model of endochondral ossification: Simulating growth of a long bone.

Mechanical loading is a crucial factor in joint and bone development. Using a computational model, we investigated the role of mechanics on cartilage growth rate, ossification of the secondary center, formation of the growth plate, and overall bone shape. A computational algorithm was developed and implemented into finite element models to simulate the endochondral ossification for symmetric and asymmetric motion in a generic diarthrodial joint. Under asymmetric loading condition the secondary center ossifies asymmetrically leaning toward the external load and results in tilted growth plate. Also the mechanics seems to have greater influence in the early onset of the ossification of the secondary center rather than later progression of the center. While previous models have simulated select stages of skeletal development, our model can simulate growth and ossification during the entirety of post-natal development. Such computational models of skeletal development may provide insight into specific loading conditions that cause bone and joint deformities, and the required timing for rehabilitative repair.

Predicting growth plate orientation with altered hip loading: potential cause of cam morphology.

Proximal femoral deformities can result from altered hip joint loading patterns during growth. The growth plate hyaline cartilage has low resistance to shear stress. Therefore, we hypothesized that the growth plate orients in a direction which minimizes the shear stress on its surface. A finite element model of the proximal femur was generated with a simplified flat growth plate. Hip joint forces were estimated for standing upright and standing in hip flexion. We also parametrically studied the effects of posteriorly and laterally directed loads. An algorithm was developed to predict the shape of the femoral growth plate in a plane of minimum shear (along the principal stress vectors). To characterize and compare the growth plate shapes, we represented the distance from the growth plate to a reference plane as a two-dimensional contour plot, providing information of shape and orientation across the entire surface. We also assessed the clinical measures of growth plate shape to compare our predicted growth plates with previous clinical studies data. The shape of the growth plate predicted for an upright standing load correlated closely with morphological properties of the growth plane of a typically developing child. The shape of the growth plate predicted for femoral hip flexion force was similar to the growth plate in subjects with cam morphology, a hip shape that has documented growth plate changes. The model proposed here allows for investigation of the relation between joint forces and growth plate shape, which will help predict the development of bony deformities.

The role of neutrophil-gelatinase-associated lipocalin in early diagnosis of contrast nephropathy.

Neutrophil-gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury. The aim of this study was to define a cut-off for NGAL in the early diagnosis of contrast-induced nephropathy (CIN) in patients with normal kidney function. We enrolled 121 patients with normal serum creatinine who underwent coronary angiography. NGAL was measured in urine before the procedure and 12 and 24 h afterward. CIN was defined as a 0.3 mg/dl increase in serum creatinine within 48 h after the procedure. Seven of 121 patients had CIN (5.8%). The NGAL levels in the 12- and 24-h urine samples of these patients were 30 (5-45) and 20 (15-40) ng/ml, respectively, whereas those in patients without CIN were 15 (5-45) and 15 (10-51) ng/ml, respectively (P = 0.8). In patients with CIN, the sensitivity and specificity of NGAL with a cut-off of 22.5 ng/ml were 71.4% and 57.9% in 12-h urine samples, with the negative predictive values (NPV) and positive predictive values (PPV) of 97.1% and 9.4%, respectively. In conclusion, we suggest that urine NGAL with cut-off point of 22.5 ng/ml has acceptable sensitivity and specificity for early diagnosis of CIN in patients with normal serum creatinine, but regarding NPV and PPV the best performance of this value is to rule out the CIN in patients at risk who received contrast media.

Evaluation of hematological and biochemical profiles in dairy cows with left displacement of the abomasum.

For the present study, 25 Holstein and crossbreed, 3 to 7-year-old cows diagnosed with left displacement of the abomasum and 15 healthy cattle as control groups over a period of 2 years were used. LDA diagnosis was based on clinical examinations (high-pitched bell-like sounds) and confirmed by laparoscopy. Two blood samples were collected from each case through the jugular vein including one tube containing EDTA for hematological parameters analysis and one tube without anticoagulant for biochemical analysis. Hematological parameters including Ca, P, Mg, Cl, AST, urea, and glucose concentrations were measured by routine procedures. Serum was determined by use of an atomic absorption spectrophotometer, and Na and K values were obtained using a flame photometer. The results of this study showed that Hb, percentage of PCV, total leukocytic, neutrophils, total protein count plus AST, urea, and glucose concentrations were significantly increased in the LDA cases compared to the control group, whereas a marked decrease in plasma electrolyte concentrations (hyponatremia, hypochloremia, hypokalemia, and hypocalcemia) was found in 88-92% of LDA cases. In conclusion, in the present study, it was shown that DA causes alterations in the clinical, hematological, and biochemical profiles and these alterations can be more severe when DA is concurrent with other diseases.

Effect of air pollution on onset of acute coronary syndrome in susceptible subgroups.

While long-term exposure to air pollutants is associated with an increase in heart diseases and mortality, little information is available about the short-term effects of air pollution. This case-crossover study assessed the relationship of particulate matter (PM10) and carbon monoxide (CO) levels with hospital admission for acute coronary syndrome in Tehran, Islamic Republic of Iran. We interviewed 250 patients with a first episode of acute coronary syndrome and obtained data from hospital records and Tehran Air Quality Control Company. The risk of acute coronary syndrome was significantly associated with elevated concentrations of CO the day before the event (OR 1.18; 95% CI: 1.03-1.34) but not significantly with PM10 (OR 1.00; 95% CI: 0.99-1.02). Stratification by age, sex, diabetes, hypertension and smoking status did not affect the results, but women were more susceptible than men to CO levels (OR for women/men 1.68; 95% CI: 1.25-2.26).

Effect of air pollution on onset of acute coronary syndrome in susceptible subgroups

While long-term exposure to air pollutants is associated with an increase in heart diseases and mortality, little information is available about the short-term effects of air pollution. This case-crossover study assessed the relationship of particulate matter [PM[10]] and carbon monoxide [CO] levels with hospital admission for acute coronary syndrome in Tehran, Islamic Republic of Iran. We interviewed 250 patients with a first episode of acute coronary syndrome and obtained data from hospital records and Tehran Air Quality Control Company. The risk of acute coronary syndrome was significantly associated with elevated concentrations of CO the day before the event [OR 1.18; 95% CI: 1.03-1.34] but not significantly with PM[10] [OR 1.00; 95% CI: 0.99-1.02]. Stratification by age, sex, diabetes, hypertension and smoking status did not affect the results, but women were more susceptible than men to CO levels [OR for women/men 1.68; 95% CI: 1.25-2.26]

Alterations of the perivascular dystrophin-dystroglycan complex following brain lesions: an immunohistochemical study in rats.

Dystroglycan is a laminin receptor, which with dystrophins and other components forms the dystrophin-dystroglycan complex. It has an important role in the formation of gliovascular connections, cerebral vascularisation and blood-brain barrier. Dystroglycan consists of two sub-units, α and ß. Previous studies demonstrated that the ß-dystroglycan immunoreactivity of cerebral vessels temporarily disappeared in the area adjacent to the lesion, whereas the vascular laminin which is not immunoreactive in the intact brain became detectable. The present study extends these investigations over other components of the complex: utrophin, α1-syntrophin and α1-dystrobrevin. The experiments were performed on adult rats. The lesions were stab wounds or cryogenic lesions in deep ketamine-xylasine narcosis. Following survival periods 2 to 30 days, the animals were perfused and floating brain sections were processed for fluorescent immunohistochemistry. The α1-dystrobrevin, like ß-dystroglycan, vanished temporarily around the lesion. The immunoreactivity of utrophin changed in a similar way to that of laminin. In intact brains they were confined to the entering segments of the vessels and to the circumventricular organs. Following lesions their immunoreactivity manifested in the vessels around the lesions. However, utrophin followed laminin with a delay: their peaks were about POD (postoperative days) 21 and 7, respectively. Only immunoreactivity of α1-syntrophin appeared in the reactive astrocytes, peaking at POD 14. Double-labeling proved its co-localization with GFAP. Cryogenic lesions had similar immunohistochemical effects, but provided more suitable samples for Western blot analysis, which proved the altered levels of α1-dystrobrevin and α1-syntrophin. The phenomena may help to monitor the post-lesion vascular processes and the alterations of the gliovascular connections.

Cardiopulmonary complications induced by Iranian Mesobuthus eupeus scorpion venom in anesthetized rabbits

Scorpion envenomation is a life-threatening condition, especially in children and elderly individuals affected by respiratory and cardiovascular diseases. In this study, the toxic effects of median lethal dose (LD50) injections of Mesobuthus eupeus (Me) venom on the heart and lungs of anesthetized rabbits were investigated. Six rabbits were selected and alterations in their electrocardiogram, heart rate, respiration and blood pressure before and after venom injection were recorded. Cardiac troponin T (cTnT), creatinine kinase muscle-brain fraction (CK-MB) and lactate dehydrogenase (LDH) were measured at 0, 1 and 3 hours after envenomation and pathology studies were carried out postmortem. All the animals showed signs and symptoms of envenomation within 40 minutes and died 3 to 3.5 hours after venom injection. Pathology studies revealed alveolar edema in 100 percent of the rabbits and myocardial infarction in 16 percent. The main histopathological changes were myocytolysis, coagulation necrosis, focal hemorrhage, thrombus formation both in myocardium and on endocardial surfaces as well as inflammatory infiltrates in the heart and hemorrhage, vascular thrombus and interstitial inflammation in the lungs. ECG monitoring of rabbits showed ST elevation, ST depression and inverted T and Q waves. In addition, although cTnT levels increased in 16 percent of the animals and serum LDH was also augmented, none of these changes was statistically significant. The enzyme CK-MB also did not show any change after Me venom injection. In conclusion, the results of this study showed that Me venom killed animals in less than 3.5 hours through severe pulmonary damage and it appears that the deaths could not be attributed to cardiovascular lesions. Therefore, Me venom effects on the lungs are so important that they appear to be independent of heart damage.(AU)

Prevalence of left main coronary artery disease among patients with ischemic heart disease: insights from the Tehran Angiography Registry.

AIM: This study was designed to investigate the prevalence of left main coronary artery (LMCA) significant stenosis among patients with stable angina (SA) or acute coronary syndromes (ACSs) and to assess the influence of demographic and clinical profiles on these findings. METHODS: A review of the Angiography Registry demonstrated that 18137 patients had SA or ACSs. The patients' characteristics were compared in subgroups with and without LMCA disease. RESULTS: Significant and minimal LMCA stenoses were found in 659 (3.6%) and 1157 (6.4%) patients, respectively. An unprotected LMCA disease was estimated in 609 (3.4%) subjects. A cumulative Logit Model analysis revealed the male gender (odds ratio [OR]=1.480, 95% confidence interval [CI]=1.287 to 1.703; P<0.001), diabetes mellitus (OR=1.158, 95% CI=1.029 to 1.303; P=0.015), dyslipidemia (OR=1.125, 95% CI=1.001 to 1.265; P=0.048), and aging (OR=1.028, 95% CI=1.022 to 1.034; P<0.001) as the independent predictors of LMCA stenosis with coexistent diseases in the rest of the coronary arteries. In the patients with normal or minimal stenoses of the other coronary arteries, cigarette smoking (OR=3.749, 95% CI=1.698 to 8.070) was found to be the independent risk factor of isolated LMCA disease. Luminal stenosis >50% in the right coronary artery, the left circumflex artery, and the left anterior descending artery was significantly more frequent in association with LMCA disease. CONCLUSIONS: The patients with LMCA disease were more likely to be male, older, and have diabetes mellitus or dyslipidemia, whereas cigarette smoking was found as an independent predictor of isolated LMCA. There was a strong correlation between the severity of LMCA stenosis and coexistent diseases in the rest of the coronary arteries.

Folate, vitamin B12 and homocysteine status in women of childbearing age: baseline data of folic acid wheat flour fortification in Iran.

BACKGROUND: Folic acid fortification implemented mandatorily in many countries has been associated with significant increase in blood folate concentrations and reduction in the prevalence of neural tube defects. However, there are controversial findings on the probability of vitamin B(12) deficiency being masked in the population after folic acid fortification. Baseline data on folate and vitamin B(12) status are necessary before mandatory flour fortification is implemented. OBJECTIVES: To assess dietary intake of folate and vitamin B(12) and to determine blood concentrations of folate, vitamin B(12) and homocysteine in women of childbearing age as baseline data regarding folic acid fortification in Iran. METHODS: A descriptive cross-sectional survey was performed with 579 healthy women as a representative sample of the Golestan province. Fasting blood samples were taken and dietary (24-hour recall), health and sociodemographic data were collected with an interview. Serum concentrations of folate and vitamin B(12) were measured with radioimmunoassay, and plasma homocysteine concentrations were assessed by high-performance liquid chromatography with fluorescence detection. RESULTS: Mean serum concentrations of folate and vitamin B(12) were 13.6 nmol/l (95% CI 12.8-14.4) and 194.4 pmol/l (95% CI 183.8-205.0), respectively. Inadequate serum folate levels were present in 14.3% of the women and 22.7% had serum vitamin B(12) levels below normal. Mean plasma homocysteine concentration was 12.6 micromol/l (95% CI 12.1-13.2) and hyperhomocysteinemia was observed in 38.3% of the women. Mean daily intake of folate and vitamin B(12) was 198.3 microg (95% CI 185.4-211.3) and 2.6 microg (95% CI 1.9-3.2), respectively. Folate intake from food was positively correlated with serum folate concentrations (r = 0.084, p < 0.05) and inversely correlated with plasma homocysteine concentrations (r = -0.115, p < 0.01). CONCLUSIONS: An insufficient vitamin B(12) as well as folate status is present in Iranian women of childbearing age. The final evaluation will be carried out 18 months after flour fortification and the results will be compared with baseline data obtained from the present study in order to show the efficacy and safety of folic acid fortification in Iran.

Early mortality predictors in coronary artery bypass grafting patients required intra-aortic balloon pump in perioperative and postoperative periods.

AIM: The intra-aortic balloon pump (IABP) is commonly used for decreasing myocardial oxygen demand by systolic unloading in perioperative heart failure. The aim of this study was to determine perioperative prognostic factors for in-hospital mortality in coronary artery bypass grafting patients who received the intraaortic balloon pump. METHODS: A total of 271 patients who underwent coronary artery bypass grafting and received intra-aortic balloon pump perioperatively between January 2002 and September 2006 were studied. The preoperative, operative and postoperative risk factors for early death were evaluated. RESULTS: Early mortality rate in the study population was 17.3%. From variables entered into multivariate logistic regression the following parameters were identified as prognostic factors for early death: left main disease, diabetes, postoperative renal failure and cardiac arrest (P<0.05). The minor and major intra-aortic balloon pump related complications were not significant in univariate and multivariate analysis and its rate was 3.6%. CONCLUSION: According to our study the mortality of IABP group is low compared to other studies, as well as IABP-associated complications. Also it revealed that there is no correlation between IABP-associated complications and early mortality.

The effect of gender on the pharmacokinetics of verapamil and norverapamil in human.

The effects of gender on the pharmacokinetics of verapamil and its active metabolite, norverapamil, following single oral dose (80 mg, Isoptin) to 12 healthy male (mean age: 25.75+/-2.42 years, mean body weight: 70.59+/-9.94 kg) and 12 healthy female subjects (mean age: 24.08+/-2.84 years, mean body weight: 56.67+/-5.23 kg) were investigated in the present study. Plasma concentrations of verapamil and norverapamil were analysed using a modified high-pressure liquid chromatography method. Pharmacokinetic parameters were calculated by non-compartmental analysis for each subject. For verapamil the half-life (t1/2) and mean residence time (MRT) were significantly shorter in women than men (p<0.01 and p<0.05, respectively). For other pharmacokinetic parameters of verapamil there were no significant differences between males and females. For norverapamil, t1/2, MRT and time to reach to the maximum plasma concentration (Tmax) showed statistically significant differences between the two genders. The AUC(0-24) and AUC(0-infinity) ratios of norverapamil to verapamil were also calculated. The ratios were significantly higher in women compared with men. These observations indicate that the elimination rate of verapamil is faster in women than men which may be attributed to the higher activity of CYP3A4 or lower activity of P-glycoprotein in women compared with men. A contribution of both factors in the appearance of gender differences in verapamil pharmacokinetics is also possible.

Adrenal function in subgroups of the PCO syndrome assessed by a long ACTH test.

Fifteen patients with the polycystic ovarian (PCO) syndrome were classified into Group A (n = 6) and Group B (n = 9) based on their LH responses to LHRH before and at 44 and 92h after administration of oestradiol benzoate. Adrenal function in both groups was assessed by comparing the hormone responses to ACTH (0.5mg twice daily for 4 days) with those obtained in nine normally ovulating women during the early follicular phase of their cycles. In Group A patients there was no significant difference from normals in the serum concentration of dehydroepiandrosterone sulphate (DHAS), 17 alpha-hydroxy-progesterone (17-OHP) or androgens (testosterone and dihydrotestosterone). In contrast, the serum concentrations in Group B were significantly higher (P less than 0.01) for each of these steroids before ACTH, and remained higher at 2 and 4 days for DHAS, but not for the other two steroids. The concentration of oestrone was significantly higher (P less than 0.05) in Group B patients before, and 2 days after, ACTH, while in Group A patients higher concentrations (P less than 0.02) were found only after 2 days. The concentrations of oestradiol, on the other hand, were not different from normal in either group before ACTH and became lower than normal in both groups at 2 days and remained lower at 4 days in Group B. The concentration of cortisol was within the normal range throughout in Group A, but was lower than normal after 4 days in Group B patients (P less than 0.05). The ratios between the sums of concentrations of DHAS to cortisol on days 2 and 4 (P less than 0.001) or 17-OHP to cortisol (P less than 0.05) were elevated in Group B compared with normal subjects. LH, FSH and prolactin values were normal throughout in Group A, but in Group B patients the mean value for LH was significantly elevated before ACTH and at 4 days after ACTH (P less than 0.02).