Olfactory impairment in Parkinson's disease and white matter abnormalities in central olfactory areas: A voxel‐based diffusion tensor imaging study

Olfactory dysfunction is known to occur before the appearance of the classical motor signs in Parkinson's disease (PD) and diffusion tensor imaging (DTI) studies in PD have reported fractional anisotropy (FA) reductions in the early disease stages. We aimed to investigate the relationship between olfactory dysfunction and white matter (WM) FA of central olfactory areas in early PD. Twenty‐four patients at Hoehn and Yahr stages I and II and 24 healthy controls matched by age, gender and years of education participated in this study. DTI was acquired at a 3 Tesla scanner and odor identification was assessed using the University of Pennsylvania Smell Identification Test (UPSIT). We performed FA voxelwise group comparisons in the central olfactory structures using tract‐based spatial statistics (TBSS) and correlation analyses between FA values in these central olfactory areas and UPSIT scores. Patients with severe microsmia (UPSIT between 19 and 25) and anosmia (UPSIT lower or equal to 18) had lower FA values than PD patients with mild/moderate or no olfactory dysfunction (UPSIT between 26 and 40) and healthy controls in the WM adjacent to gyrus rectus. In addition, patients with anosmia had reduced FA in the WM surrounding primary olfactory areas in comparison with healthy controls. FA values in the WM adjacent to primary olfactory cortex and right gyrus rectus correlated with UPSIT scores in the PD group. This study demonstrates, for the first time, that microstructural WM reductions are present in the central olfactory system of early stage PD patients and that these reductions are associated with reduced ability to smell. © 2010 Movement Disorder Society     

Hematologic toxicities of small molecule tyrosine kinase inhibitors

Small molecule tyrosine kinase inhibitors (TKIs) are potent anti-cancer targeted therapies. TKIs are considered safe and efficacious therapeutic modalities, and are generally tolerated well. However, they are associated with certain side effects including hematologic toxicities such as anemia, macrocytosis, neutropenia, thrombocytopenia, hemolytic anemia, bone marrow aplasia and necrosis. Thrombotic microangiopathy, arterial thromboembolism and splenic infarction can also occur following treatment with TKIs. Cytopenias are the most common adverse effects associated with these agents, and other hematologic toxicities are not frequent. It is essential for clinicians to monitor patients closely, and recognize those side effects as early as possible, in order to improve efficacy of small molecule TKIs and optimize outcomes. This article summarizes hematologic toxicities associated with the commonly used small molecule TKIs. It also provides practical strategies for the management of these toxicities.     

Detection of Duchenne/Becker muscular dystrophy carriers in a group of Iranian families by linkage analysis

This study determines the value of linkage analysis using six RFLP markers for carrier detection and prenatal diagnosis in familial DMD/BMD cases and their family members for the first time in the Iranian population. We studied the dystrophin gene in 33 unrelated patients with clinical diagnosis of DMD or BMD. Subsequently, we determined the rate of heterozygosity for six intragenic RFLP markers in the mothers of patients with dystrophin gene deletions. Finally, we studied the efficiency of linkage analysis by using RFLP markers for carrier status detection of DMD/BMD. In 63.6% of the patients we found one or more deletions. The most common heterozygous RFLP marker with 57.1% heterozygosity was pERT87.15Taq1. More than 80% of mothers in two groups of familial or non-familial cases had at least two heterozygous markers. Family linkage analysis was informative in more than 80% of the cases, allowing for accurate carrier detection. We found that linkage analysis using these six RFLP markers for carrier detection and prenatal diagnosis is a rapid, easy, reliable, and inexpensive method, suitable for most routine diagnostic services. The heterozygosity frequency of these markers is high enough in the Iranian population to allow carrier detection and prenatal diagnosis of DMD/BMD in more than 80% of familial cases in Iran.     

A randomized, double-blind clinical trial comparing the effects of continuous and pulsed ultrasound in patients with chronic rhinosinusitis

The objective of the present study was to compare the effects of continuous ultrasound (CUS) with pulsed ultrasound (PUS) in patients with chronic rhinosinusitis (CRS). In this prospective, randomized, double-blind, parallel group study, 40 patients (10 losses) with CRS participated. Patients received either continuous or pulsed (1:9) 1 MHz ultrasound (US) using a US head of 1?cm2 at 1 W/cm2 and 0.5 W/cm2 for the maxillary and frontal sinuses, respectively. Treatment was performed in 10 sessions, 3 days per week, with US given every other day. The primary outcome measure was percent improvement in the Sinusitis Symptom Score. Measurements were taken before and after 10 treatment sessions. The patients were followed up monthly for 2 months. After treatment, both groups improved significantly on the Sinusitis Symptoms Score. Patients who received PUS had significantly decreased total symptom scores compared with patients receiving CUS (mean change 9.8 vs. 5.6, p?=?0.049). The percent improvement in the Sinusitis Symptom Score between the PUS group (65.2 SD 23.1) and the CUS group (43.9 SD 40.7) was not statistically significant (p?=?0.09). The effect size for each treatment was large; PUS: d?=?3.92 and CUS: d?=?1.93. Symptom improvement in both groups was similar at the 2-month follow-up. These results support the use of therapeutic US for CRS. This pilot study gives only marginal evidence to favor PUS over CUS.     

Positive effect of septimeb? on mortality rate in severe sepsis: a novel non antibiotic strategy

Background

Septimeb is a new herbal-derived remedy, recently approved for its potential immunomodulatory effects. Regarding the key role of immune system in the pathogenesis of severe sepsis and lack of any standard treatment for improving survival of these patients; we evaluated the effect of Septimeb -as an adjutant to standard treatment-on inflammatory biomarkers and mortality rates in patients with severe sepsis.

Methods

In this multicenter, randomized, single-blind trial, we assigned patients with severe sepsis and Acute Physiology and Chronic Health Evaluation (APACHE II) score of more than 20 to receive standard treatment of severe sepsis (control group) or standard treatment plus Septimeb. This group was treated with Septimeb for 14 days then followed up for another14 days. APACHE score, Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score (SAPS) were calculated daily. Blood samples were analyzed for interleukin 2 tumor necrosis factor-α, total antioxidant power, platelet growth factor and matrix metalloproteinase 2.

Results

A total of 29 patients underwent randomization (13 in control group and 16 in Septimeb group). There was significant difference between the Septimeb and control group in the 14 days mortality rate (18.8% vs. 53.85 respectively, P=0.048). Compared to control group, Septimeb was significantly effective in improving SAPS (P= 0.029), SOFA (P=0.003) and APACHE II (P=0.008) scores. Inflammatory biomarkers didn’t change significantly between the two groups (P>0.05).

Conclusion

Septimeb reduces mortality rates among patients with severe sepsis and it could be added as a safe adjutant to standard treatment of sepsis.     

Phytochemical screening and evaluation of cardioprotective activity of ethanolic extract of Ocimum basilicum L. (basil) against isoproterenol induced myocardial infarction in rats

Background and the purpose of the study

The objectives of the present study were phytochemical screening and study of the effects of ethanolic extract of aerial parts of Ocimum basilicum (basil) on cardiac functions and histopathological changes in isoproterenol-induced myocardial infarction (MI).

Methods

The leaves of the plant were extracted with ethanol by maceration and subjected to colorimetry to determine flavonoids and phenolic compounds. High-performance TLC analysis and subsequent CAMAG''s TLC scanning were performed to quantify rosmarinic acid content. Wistar rats were assigned to 6 groups of normal control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg of the extract two times per day concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day) for 2 consecutive days was used to induce MI.

Results

Phytochemical screening indicated the presence of phenolic compounds (5.36%) and flavonoids (1.86%). Rosmarinic acid was the principal phenolic compound with a 15.74% existence. The ST-segment elevation induced by isoproterenol was significantly suppressed by all doses of the extract. A severe myocardial necrosis and fibrosis with a sharp reduction in left ventricular contractility and a marked increase in left ventricular end-diastolic pressure were seen in the isoproterenol group, all of which were significantly improved by the extract treatment. In addition to in-vitro antioxidant activity, the extract significantly suppressed the elevation of malondialdehyde levels both in the serum and the myocardium.

Conclusion

The results of the study demonstrate that Ocimum basilicum strongly protected the myocardium against isoproterenol-induced infarction and suggest that the cardioprotective effects could be related to antioxidative activities.     

Histopathologic characteristics of inferior turbinate vs ethmoidal polypin chronic rhinosinusitis

It seems apparently that the 2 separate anatomical areas (nasal cavity and paranasal sinus mucosa) are indeed one single unit with an identical behavior during inflammatory process. Similar histopathologic evidence in long-term condition could emphasize on the concept of rhinosinusitis in patients with inflammatory paranasal sinus disease. Prospective study was performed on 50 consecutive patients with polyposis in 2 different groups, one with and the other without asthma. Inferior turbine and polyp with ethmoid sinus origin were selected to compare the histopathologic findings of the surgical specimens from the 2 sites (affected sinus vs apparently unaffected nose). The general degree of inflammation, epithelial thickening, and inflammatory cell count were measured. The degree of inferior turbinate inflammation correlated with that of the ipsilateral polyp of ethmoid sinus in both groups. In addition, the total inflammatory cell count was comparable. There was no statistically significant difference in total polymorphonuclear, lymphocyte, and eosinophil count between the 2 sites in each group (P > .05). The ethmoid sinus inflammation in polypoid chronic sinusitis is accompanied by a proportionate inferior turbinate inflammation, not only in the patients with asthma but also in those with isolated sinonasal polyposis.     

Non-invasive estimation of cerebrospinal fluid pressure waveforms by means of retinal venous pulsatility and central aortic blood pressure

Current techniques used for cerebrospinal fluid pressure (CSFp) measurements are invasive. They require a surgical procedure for placement of a pressure catheter in the brain ventricles or in the brain tissue. The human eye provides direct visualisation of its physiological structures and due to its anatomical connection with CSF via the retrolaminar optic nerve it may provide accessible information about CSFp. A total of 25 subjects were included in this study. 15 subjects were used to characterise the relationship between intraocular pressure (IOP), spontaneous retinal venous pulsatility (SRVP), and CSFp. IOP was manipulated and SRVP amplitudes recorded dynamically using the dynamic vessel analyzer (DVA). The relationship between IOP and SRVP amplitude was established to estimate CSFp. Additionally Doppler blood flow velocity of the middle cerebral artery and arterial blood pressure (ABP) were acquired for all subjects. This was to compare and validate our findings with an alternative approach (ICM+) which uses these values to estimate CSFp. A CSFp waveform was extracted from central blood pressure (CBP) waveform by removing its cardiac component frequency. Furthermore to calibrate the CSFp to CBP waveform ratio, invasive CSFp, and ABP was measured from 10 subjects with brain tumours who had a range of normal to elevated CSFp (i.e., 0-30 mmHg). Results show good agreement between the two methods (correlation r (2) = 0.55) Mean estimated CSFp for the two techniques did not show any significant difference (p > 0.05). A significant correlation between CBP pulse (CBPp) and invasive CSFp pulse (CSFpp) was observed (i.e., CSFpp = 0.0654CBBp + 3.91, p < 0.01). Estimated CSFpp was calibrated to CBPp according to this relation. In conclusion, the study demonstrated a good correlation between two different methods of estimating CSFp non-invasively and may provide a novel method to estimate CSF waveforms non-invasively.