Mitral annular motion as a surrogate for left ventricular function: correlation with brain natriuretic peptide levels.

BACKGROUND: Pulsed-wave (PW) Doppler tissue velocities of the mitral annulus correlate well with Left Ventricular (LV) diastolic(D) and systolic(S) functions. Brain natriuretic peptide (BNP) levels have been shown to be elevated in patients with symptomatic LV dysfunction (Dys) and correlate to the severity of symptoms and prognosis. OBJECTIVES: To validate the accuracy of mitral annular motion (MAM) assessed by Doppler Tissue Imaging (DTI) & M-mode Echocardiography (MME) as a surrogate for determination of LV function in comparison with BNP. METHODS: A series of 133 patients with a variety of cardiac pathologies referred for echocardiography and 20 healthy age & sex matched volunteers as a control group were included the study. Ejection fraction (EF) of LV, Doppler recordings of the mitral inflow, MME and PWDTI data (from each of 4 mitral annular sites, inferior, anterior, septum and lateral) were obtained. Mean peak (S) MAM velocity (Sm), mean annular early (D) velocity (Em) by PWDTI and mean mitral annular plane (S) excursion (MAPSE) by MME were calculated by averaging of values measured at each annular site. BNP levels were measured by a rapid immunoassay and blinded to cardiologist making the assessment of LV function. RESULTS: MAPSE < 12 mm determined by MME has 90% sensitivity, 88% specificity & 89% accuracy for detection of LVEF <50%, while these values were 94%, 93% & 94% respectively for (Sm) < 8 cm/s determined by PWDTI. BNP level>75 pg/ml has 98% sensitivity, 90% specificity & 97% accuracy for detection of LV Dys either (S,D, or both). BNP levels were significantly higher in patients with combined (S & D) Dys. Than those with only (S) Dys, the later group had significantly higher BNP levels than those with only (D) Dys. (1054.5 +/- 202.3 pg/ml vs. 500 +/- 39.9 pg/ml & 500 +/- 39.9 pg/ml vs. 215.3 +/- 100.9 pg/ml respectively, P < 0.001) & each were significantly higher than control group (12.3 +/- 5.7 pg/ml, P < 0.001). Significant correlations (P < 0.001 for all) were found between BNP levels and Em (r =-0.82), Sm (r=-0.7), early transmitral (E) to Em ratio (r=0.61), MAPSE (r=-0.54), LVEF(r=-0.64) & LV end D dimension (r=0.63). CONCLUSION: MME and PWDTI used for assessment of MAM are useful methods for evaluation of LV function but parameters measured by PWDTI correlate more strongly with plasma BNP levels than those measured by MME and provide a simple, sensitive, accurate and reproducible tool for early diagnosis of LV dysfunction.     

Factors affecting shear thickening behavior of a concentrated injectable suspension of levodopa

Previous clinical studies on a subcutaneous injectable suspension of levodopa showed poor injectability into human tissue. When this formulation was rheologically characterised, a clinical shear thickening interval was observed at increased shear rates. The formulation parameters that contributed to this rheological behavior were systematically evaluated with the aim of removing this flow limitation while maintaining the concentration of 60% levodopa to retain the clinical applicability. The three suspension parameters examined were: levodopa volume fraction, concentration of the HPMC suspending vehicle, and particle size distribution. Shear thickening increased with the drug concentration and the critical shear rate was inversely dependent on the drug concentration. Increasing the vehicle concentration retarded the shear thickening but increased the overall suspension viscosity. There was an increase in shear thickening with increased average particle diameter. Combinations of micronized and non-micronized particles were used to prepare bimodal particle size distributions. The rheology of these bimodal distributions resulted in removal of shear thickening. This allowed the preparation of 60% levodopa formulations that showed a range of flow characteristics spanning near Newtonian flow or shear thinning at initial injectable viscosities of about 0.6 Pa.s and final viscosities in the range of 0.1 Pa.s, alleviating the shear thickening limitation of these levodopa formulations.     

Protective drugs in acute large-dose exposure to organophosphates: a comparison of metoclopramide and tiapride with pralidoxime in rats

Weak and reversible inhibitors of cholinesterase(s), when coadministered in excess with a more potent inhibitor such as organophosphates, can act in a protective manner. The benzamide compound, metoclopramide, confers some protection (putatively via this mechanism) for cholinesterases against inhibition by paraoxon both in vitro and in vivo, after chronic small-dose exposure. Tiapride is a related benzamide. In this study, we compared the protection by metoclopramide and tiapride in rats acutely exposed to large doses of paraoxon with the therapeutic "gold standard," pralidoxime. Group 1 received 1 micromol paraoxon (approximately 75% lethal dose), Group 2 received 50 micromol metoclopramide, Group 3 received 50 micromol tiapride, Group 4 received 50 micromol pralidoxime, Group 5 received 1 micromol paraoxon + 50 micromol metoclopramide, Group 6 1 micromol paraoxon + 50 micromol tiapride, and Group 7 1 micromol paraoxon + 50 micromol pralidoxime. All substances were administered intraperitoneally. The animals were monitored for 48 h and mortality was recorded at 30 min, 1, 2, 3, 4, 24, and 48 h. Blood was taken for red blood cell acetylcholinesterase measurements at baseline, 30 min, 24, and 48 h. With the exception of Group 7, in which some late mortality was observed, mortality occurred mainly in the first 30 min after paraoxon administration with minimal changes occurring thereafter. Mortality at 30 min was 0% in the metoclopramide, tiapride, and pralidoxime groups and 73 +/- 20 (paraoxon), 65 +/- 15 (paraoxon + metoclopramide), 38 +/- 14 (paraoxon + tiapride), and 13 +/- 19 (paraoxon + pralidoxime). Mortality at 48 h was 75 +/- 18 (paraoxon), 67 +/- 17 (paraoxon + metoclopramide), 42 +/- 16 (paraoxon + tiapride), and 27 +/- 24 (paraoxon + pralidoxime). Metoclopramide does not significantly influence mortality after acute large-dose paraoxon exposure. Both tiapride and pralidoxime significantly decreased mortality in our model. The protection conferred by tiapride was significantly less than that conferred by pralidoxime at 30 min, but was not significantly different at 24 and 48 h.     

Autologous fascial sling vs polypropylene tape at short-term followup: a prospective randomized study

PURPOSE: The incidence of urinary incontinence in women of childbearing age is about 30%. Around half have stress incontinence. Many treatment modalities have been elucidated to treat stress incontinence, and among the most popular are rectus fascia sling and tension-free vaginal tape (TVT). The introduction of TVT to the urological armamentarium put a multiplicity of synthetic materials into use in the correction of stress urinary incontinence. A comparison of the impact of these 2 commonly used techniques is needed. MATERIALS AND METHODS: A total of 53 female patients older than 21 years (mean age 45.09) were randomized, using closed envelopes, to undergo TVT or rectus fascia sling. Randomization was performed after patients received spinal anesthesia. One surgeon performed the 2 types of treatment. Associated grade 2 cystocele was simultaneously corrected. Patients with bladder or urethral pathology, as well as those with cystocele greater than grade 2, were excluded from analysis. RESULTS: All 53 patients completed 6 months of followup and all had stress urinary incontinence. There were 15 patients who underwent sling surgery and 17 who underwent TVT who had concomitant grade 1 or 2 cystocele. No statistically significant difference was found between the 2 groups at baseline. Cure was accomplished in 23 of 25 (92%) with sling and in 26 of 28 (92.9%) with TVT at first followup visit (1 week). There were 7 patients who needed at least 1 extra week of catheterization in the sling group and 3 in the TVT group. No significant difference was detected in terms of post-void residual urine, symptom score, and filling and voiding parameters. At 6 months 1 patient had de novo detrusor overactivity and 7 had wound pain. Compared to those with TVT, 2 cases of sling were considered treatment failures, none had de novo overactivity and 2 had wound pain. None of the patients had symptoms suggestive of urethral erosion. CONCLUSIONS: Rectus fascia sling and TVT seem to be equally effective regarding primary outcome measure (ie cure of stress incontinence). Symptom score related to incontinence surgery as well as simultaneous correction of cystocele are comparable in the 2 groups. Fascial sling is a longer treatment process yet it is more economical. Longer followup is vital before rigorous conclusions can be drawn.     

Variables affecting initial stability of impaction grafting for hip revision

Impaction grafting allows restoration of bone stock in hip revision, but there are reports of massive early subsidence. The aim of this study was to determine prognostic factors for stem and cup migration in a group of 56 consecutive patients followed up from 1 to 5 years. Cup and stem migration was correlated with 13 predictors including stem design, stem positioning, femoral anatomy, patient characteristics, and bone graft density. All migration occurred mainly during the first 3 months after surgery. Stem alignment changed by an average of 4.8 degrees . Fifty percent of the change in stem alignment was explained by four variables: age, femoral diameter, stem design, and density of the graft at the tip of the stem. Stem subsidence averaged 2.7 mm, and cup migration averaged 3.0 mm. None of the predictors explained the wide variation of migration of the cup or distal migration of the stem. It may be necessary to determine implant stability at the time of surgery.     

The resuscitation outcome: revisit the story of the stony heart

Postresuscitation syndrome is a state of myocardial dysfunction after the restoration of circulation by successful resuscitation. Despite several advances in the field of resuscitation, the management of out-of-hospital cardiac arrest is still suboptimal. The high fatality rate shortly after successful resuscitation is mainly related to postresuscitation myocardial dysfunction. Postresuscitation myocardial stunning is reversible, while stony heart is irreversible due to prolonged unsuccessful resuscitation. This article reviews most of the published articles concerning the causes, mechanism, pathophysiology, and the updated trials for management of postresuscitation myocardial dysfunction. Further studies are warranted to highlight postresuscitation disease and its hemodynamic sequences and then to intervene according to the different phases of cardiac arrest. By modifying the conventional modalities of resuscitation together with new promising agents, the rescuers will be able to salvage the jeopardized postresuscitation myocardium and prevent its progression to the dismal stony heart. Community awareness and staff education are crucial to shorten resuscitation time and improve short-term and long-term outcomes. There is an urgent need to revise the guidelines for cardiopulmonary resuscitation in community setting, but how? It is a matter of where and when it is of enough value to be efficacious and cost-effective.     

Coeliac disease in developing countries: Middle East, India and North Africa

Following the application of simple serological tests for the diagnosis of coeliac disease (CD) in the 1980s, it gradually became clear that the prevalence of CD in different countries in the Middle East, North Africa and India is almost the same as that in Western countries. The prevalence of CD in at-risk populations in these regions is reported to range between 3 and 20% and the prevalence in people with type 1 diabetes is approximately 3-5%. Clinical manifestations of CD vary markedly with age, the duration and the extent of disease. Clinical studies showed that presentation with non-specific symptoms or no symptoms is as common in the Middle East as it is in Europe. Wheat has been the major staple food in these regions for many centuries and it is possible that the continuous and high level of exposure to wheat proteins has induced some degree of immune tolerance, leading to milder symptoms, which are misdiagnosed as irritable bowel syndrome or unexplained gastrointestinal disorders. A high index of suspicion for CD should be maintained in all developing countries for patients who present with chronic diarrhoea or iron deficiency anaemia.The best method for diagnosing CD in patients with diarrhoea is the panel of coeliac serological tests followed by small-bowel biopsy. In the absence of supplies for a gluten-free diet in Middle Eastern countries, maintaining this diet represents a real challenge to both patients and clinicians.     

Potential nonhormonal therapeutics for medical treatment of leiomyomas

Uterine leiomyomas are a common disorder resulting in significant morbidity for women and substantial economic impact on the health care system. Current therapies include conservative surgery, hysterectomy, and hormonal therapy. Conservative surgical therapy often fails because of recurrence, and hysterectomy dramatically limits reproductive options. Radiologic therapies are associated with considerable risk of morbidity and mortality and are not likely to be compatible with reproduction. Hormonal therapies such as gonadotropin-releasing hormone (GnRH) analogues or progestins with or without estrogen are utilized by many patients, but long-term use of either is often responsible for unacceptable morbidity and hormonal therapies are not compatible with reproduction. Newer hormonal alternatives such as progesterone antagonists and selective agonists as well as "add-back" estrogen therapy in addition to GnRH analogues have been developed and show promise. However, no hormonal therapy that significantly alters estrogen and progesterone production or function is likely to be compatible with reproduction. Thus, it is important to develop novel nonhormonal therapies for medical treatment of leiomyomas. Other laboratories have evaluated pirfenidone, halofuginone, heparin, and interferon-alpha (IFN-alpha). Recent work in our laboratory suggests potential use of two additional classes of compounds, thiazolidinediones and tocopherol analogs. The rationale, evidence, and potential for the use of each of these compounds in the treatment of leiomyomas are discussed.     

Pretreatment cystatin C in children with malignancy: can it predict chemotherapy-induced glomerular filtration rate reduction during the induction phase?

BACKGROUND: Monitoring of kidney function is essential during chemotherapy. Serum creatinine is of limited value in early detection of renal insufficiency. The cystatin C level has been proved to be a good marker for detection of mild reduction in glomerular filtration rate. PURPOSE: To evaluate the validity of the pretreatment serum cystatin C level in predicting significant reduction of the glomerular filtration rate during the induction phase of chemotherapy. PATIENTS AND METHODS: Serum levels of cystatin C and creatinine and corrected creatinine clearance were assessed in 34 children with different types of malignancy just before the start of chemotherapy and again in 33 of them 1 month later. Patients were compared with 14 healthy controls of matched age and sex. RESULTS: Before chemotherapy, all patients when compared with controls had normal levels of cystatin C (P = 0.1) and creatinine (P = 0.62) and normal corrected creatinine clearance (P = 0.76). One month after chemotherapy, patients showed a significant increase in their cystatin C levels (P < 0.001) and a significant decrease in their corrected creatinine clearance (P < 0.001). However, creatinine levels did not change significantly (P = 0.65). Corrected creatinine clearance negatively correlated significantly with both cystatin C and creatinine levels (r = -0.622, P < 0.001; r = -0.346, P = 0.045, respectively) before chemotherapy and also 1 month after chemotherapy (r = -0.577, P < 0.001; r = -0.45, P = 0.009, respectively). When pretreatment levels of cystatin C and creatinine were used to predict patients who developed a reduction in corrected creatinine clearance of more than 20% after therapy, only the cystatin C level was statistically significant (P = 0.03). A cutoff point of 0.57 mg/L with sensitivity of 77.8%, specificity of 63%, and overall accuracy of 74% was suggested. CONCLUSIONS: Children with malignant diseases develop significant reduction in their glomerular filtration rate during the induction phase of chemotherapy, although their serum creatinine level may not change significantly. Cystatin C, as a more sensitive marker than creatinine for the assessment of glomerular filtration rate, can be used to predict patients who would have a higher risk of renal impairment during the induction phase of chemotherapy and who thus would require more frequent renal function assessment to consider adjustment of the chemotherapy dose if indicated.     

Successful percutaneous coil occlusion of a large pulmonary arteriovenous malformation

Pulmonary arteriovenous malformation is one of the rarest congenital anomalies of cardiovascular system. We present a case of 30-year-old female with a large pulmonary arteriovenous malformation (PAVM) arising from the right lower pulmonary artery and draining to the left atrium. She underwent successful embolization using three detachable Cook coils.