Accuracy of in vivo microCT imaging in assessing the microstructural properties of the mouse tibia subchondral bone.

Osteoarthritis (OA) is one of the most common musculoskeletal diseases. OA is characterized by degeneration of the articular cartilage as well as the underlying subchondral bone. Post-traumatic osteoarthritis (PTOA) is a subset of OA caused by mechanical trauma. Mouse models, such as destabilization of the medial meniscus (DMM), are useful to study PTOA. Ex vivo micro-Computed Tomography (microCT) imaging is the predominant technique used to scan the mouse knee in OA studies. Nevertheless, in vivo microCT enables the longitudinal assessment of bone microstructure, reducing measurement variability and number of animals required. The effect of image resolution in measuring subchondral bone parameters was previously evaluated only for a limited number of parameters. The aim of this study was to evaluate the ability of in vivo microCT imaging in measuring the microstructural properties of the mouse tibia trabecular and cortical subchondral bone, with respect to ex vivo high resolution imaging, in a DMM model of PTOA. Sixteen male C57BL/6J mice received DMM surgery or sham operation at 14 weeks of age (N=8 per group). The right knee of each mouse was microCT scanned in vivo (10.4µm voxel size) and ex vivo (4.35µm voxel size) at the age of 26 weeks. Each image was aligned to a reference image using rigid registration. The subchondral cortical bone plate thickness was measured at the lateral and medial condyles. Standard morphometric parameters were measured in the subchondral trabecular bone. In vivo microCT imaging led to significant underestimation of bone volume fraction (-14%), bone surface density (-3%) and trabecular number (-16%), whereas trabecular thickness (+3%) and separation (+5%) were significantly overestimated. Nevertheless, most trabecular parameters measured in vivo were well correlated with ex vivo measurements (R2 = 0.69-0.81). Degree of anisotropy, structure model index and connectivity density were measured in vivo with lower accuracy. Excellent accuracy was found for cortical thickness measurements. In conclusion, this study identified what bone morphological parameters can be reliably measured by in vivo microCT imaging of the subchondral bone in the mouse tibia. It highlights that this approach can be used to study longitudinal effects of diseases and treatments on the subchondral cortical bone and on most subchondral trabecular bone parameters, but systematic over- or under-estimations should be considered when interpreting the results.

Assessing cross-resistance within the pyrethroids in terms of their interactions with key cytochrome P450 enzymes and resistance in vector populations.

BACKGROUND: It is important to understand whether the potential impact of pyrethroid resistance on malaria control can be mitigated by switching between different pyrethroids or whether cross-resistance within this insecticide class precludes this approach. METHODS: Here we assess the relationships among pyrethroids in terms of their binding affinity to, and depletion by, key cytochrome P450 enzymes (hereafter P450s) that are known to confer metabolic pyrethroid resistance in Anopheles gambiae (s.l.) and An. funestus, in order to identify which pyrethroids may diverge from the others in their vulnerability to resistance. We then investigate whether these same pyrethroids also diverge from the others in terms of resistance in vector populations. RESULTS: We found that the type I and II pyrethroids permethrin and deltamethrin, respectively, are closely related in terms of binding affinity to key P450s, depletion by P450s and resistance within vector populations. Bifenthrin, which lacks the common structural moiety of most pyrethroids, diverged from the other pyrethroids tested in terms of both binding affinity to key P450s and depletion by P450s, but resistance to bifenthrin has rarely been tested in vector populations and was not analysed here. Etofenprox, which also lacks the common structural moiety of most pyrethroids, diverged from the more commonly deployed pyrethroids in terms of binding affinity to key P450s and resistance in vector populations, but did not diverge from these pyrethroids in terms of depletion by the P450s. The analysis of depletion by the P450s indicated that etofenprox may be more vulnerable to metabolic resistance mechanisms in vector populations. In addition, greater resistance to etofenprox was found across Aedes aegypti populations, but greater resistance to this compound was not found in any of the malaria vector species analysed. The results for pyrethroid depletion by anopheline P450s in the laboratory were largely not repeated in the findings for resistance in malaria vector populations. CONCLUSION: Importantly, the prevalence of resistance to the pyrethroids α-cypermethrin, cyfluthrin, deltamethrin, λ-cyhalothrin and permethrin was correlated across malaria vector populations, and switching between these compounds as a tool to mitigate against pyrethroid resistance is not advised without strong evidence supporting a true difference in resistance.

Fast-track rapid warfarin reversal for elective surgery: extending the efficacy profile to high-risk patients with cancer.

Periprocedural management of patients on long-term warfarin therapy remains a common and important clinical issue, with little high-quality data to guide this complex process. The current accepted practice is cessation of warfarin five days preoperatively, but this is not without risk and can be complicated, particularly if bridging is required. An alternative method utilising low-dose intravenous vitamin K the day before surgery has been shown previously to be efficacious, safe and convenient in an elective surgical population receiving chronic warfarin therapy. The efficacy and utility of this 'fast-track' warfarin reversal protocol in surgical patients with cancer, who were at high risk of both thromboembolism and bleeding was investigated in a prospective, single-arm study at a dedicated cancer centre. Seventy-one patients underwent 82 episodes of fast-track warfarin reversal (3 mg intravenous vitamin K 18 to 24 hours before surgery). No patient suffered an adverse reaction to intravenous vitamin K, all but one achieved an International Normalized Ratio =1.5 on the day of surgery, and no surgery was deferred. Assays of vitamin K-dependent factor levels pre- and post-vitamin K demonstrated restoration of functional activity to within an acceptable range for surgical haemostasis. While this alternative method requires further validation in a larger prospective randomised study, we have now extended our use of fast-track warfarin reversal using vitamin K to patients with cancer, on the basis of our experience of its safety, convenience, reliability and efficacy.

Inhibition of iPLA2 ß and of stretch-activated channels by doxorubicin alters dystrophic muscle function.

BACKGROUND AND PURPOSE: Chronic elevation in intracellular Ca(2+) concentration participates in death of skeletal muscle from mdx mice, a model for Duchenne muscular dystrophy (DMD). Candidate pathways mediating this Ca(2+) overload involve store-operated channels (SOCs) and stretch-activated channels (SACs), which are modulated by the Ca(2+) -independent form of PL A2 (iPLA2 ). We investigated the effect of doxorubicin (Dox), a chemotherapeutic agent reported to inhibit iPLA2 in other systems, on the activity of this enzyme and on the consequences on Ca(2+) handling and muscle function in mdx mice. EXPERIMENTAL APPROACH: Effects of Dox on iPLA2 activity, reactive oxygen species production and on Ca(2+) influx were investigated in C2C12 and mdx myotubes. The mechanism of Dox-mediated iPLA2 inhibition was evaluated using purified 6x histidine-tagged enzyme. Aequorin technology was used to assess Ca(2+) concentrations underneath the plasma membrane. Isolated muscles were exposed to fatigue protocols and eccentric contractions to evaluate the effects of Dox on muscle function. KEY RESULTS: Dox at 1-30 µM inhibited iPLA2 activity in cells and in the purified enzyme. Dox also inhibited SAC- but not SOC-mediated Ca(2+) influx in myotubes. Stimulated elevations of Ca(2+) concentrations below the plasmalemma were also blocked. Exposure of excised muscle to Dox was not deleterious to force production and promoted recovery from eccentric contractions. CONCLUSIONS AND IMPLICATIONS: Dox showed efficacy against targets known to play a role in the pathology of DMD, namely iPLA2 and SAC. The potent SAC inhibitory effect of Dox is a novel finding that can explain partly the cardiomyopathy seen in chronic anthracycline treatment.

Prevalence and risk factors for spousal violence among women attending health care centres in Alexandria, Egypt.

We conducted a cross-sectional survey to determine the prevalence of, and factors affecting, spousal violence among 3271 ever-married women attending 12 randomly selected family health centres in Alexandria Governorate. More than three-quarters of the participants (77%) reported experiencing spousal violence during their marital life. Emotional violence was the most common type reported (71.0%), followed by physical (50.3%), economic (40.8%) and sexual (37.1%) violence. The study confirms the high prevalence of spousal violence across all socioeconomic strata. Logistic regression analysis indicated large family size, divorce or separation, low educational attainment of husband, smoking habit and drug use in husband, husband's psychological status and history of exposure to physical violence during adolescence were associated with spousal violence. This high rate of spousal violence highlights the urgent need for government and civil society to address the issue, which hinders progress toward Egypt's development goals.

Prevalence and risk factors for spousal violence among women attending health care centres in Alexandria, Egypt

We conducted a cross-sectional survey to determine the prevalence of, and factors affecting, spousal violence among 3271 ever-married women attending 12 randomly selected family health centres in Alexandria Governorate. More than three-quarters of the participants [77%] reported experiencing spousal violence during their marital life. Emotional violence was the most common type reported [71.0%], followed by physical [50.3%], economic [40.8%] and sexual [37.1%] violence. The study confirms the high prevalence of spousal violence across all socioeconomic strata. Logistic regression analysis indicated large family size, divorce or separation, low educational attainment of husband, smoking habit and drug use in husband, husband's psychological status and history of exposure to physical violence during adolescence were associated with spousal violence. This high rate of spousal violence highlights the urgent need for government and civil society to address the issue, which hinders progress toward Egypt's development goals

Views of undergraduate students on objective structured clinical examination in neurology: a preliminary report.

OBJECTIVE: Obtain the undergraduate medical students' evaluation of an objective structured clinical examination (OSCE) formed by two stations in neurology. METHODS: The fifth-year medical students taking the neurology course at King Faisal University during the first rotation of academic year 1420-1421H (2000-2001G) made the evaluation. The time for each station was seven minutes. After finishing the examination, each student completed a six-item questionnaire on coverage, question clarity, time, patients, educational usefulness and organization of the examination with yes, no or don't know responses. RESULTS: A total of 48 students (30 males and 18 females) took the examination. The average time to complete the examination for a group of 16 students was 2 hours. The responses were positive for clarity of questions and organization of the examination 41(85%), and allotted time 36(75%). Thirty-two students (67%) found the structured examination a useful educational experience. About half the students expressed their concern about the coverage of taught material and the number of patients seen in the examination as representative of those seen during the course, and 11 students (23%) requested more time. CONCLUSIONS: The students' response to the use of the structured clinical examination as an objective tool for evaluation of clinical skills in neurology was favorable and comparable to reports from other parts of the world. Improvement is required in the number of patients, coverage and allotted time to optimize outcome by improving content validity and reducing stress on participating patients.

Clinical pattern of newly-diagnosed seizures in Saudi Arabia: a prospective study of 263 children.

The clinical patterns, including history, examination, and electroencephalographic (EEG) and computed tomography (CT) findings were examined prospectively in 263 children (153 boys, 110 girls) with newly diagnosed recurrent seizures. The overall mean age was 4. 2 years, with a range of 0.05-13 years. The age of onset was within the first year of life in 128 (48.7%) of the patients. Hypoxic-ischemic encephalopathy (14.8%), febrile seizures (9.1%) and developmental delay (4.6%) were the predominant signs in this age group. Consanguinity of the parents was present in 29.7% cases. The main EEG abnormalities were epileptiform activity, which was generalized in 133 (50.6%) and focal in 80 (30.4%). Other abnormalities included slow wave activity in 41 (15.6%) and hypsarrhythmia in 3 (1.1%). The main seizure types were generalized in 60.4% and partial in 32.7%. The types of epileptic syndromes included localization-related (28.1%), generalized (23.2%), undetermined (37.4%) and (special) syndromes 11.4%. The cranial CT findings were normal in 60.5%, and the predominant abnormality was cerebral atrophy in 25.3%. The pattern of seizure types and the peak presentation in early childhood are comparable to those in western reports.

A rapid supercritical fluid extraction method for the qualitative detection of 2-alkylcyclobutanones in gamma-irradiated fresh and sea water fish.

2-Alkylcyclobutanones are routinely used as chemical markers for irradiated foods containing lipids. However, current extraction procedures (soxhlet-Florisil chromatography) for the isolation of these markers involve a long and tedious clean-up regime prior to GC-MS identification. A simple and rapid method for the isolation of these markers using carbon dioxide as a super critical fluid is described for low lipid content fish samples (fresh and sea water) irradiated up to 8kGy. The presence of 2-dodecylcyclobutanone (2-DCB), a radiolytic marker, was confirmed in all irradiated fish samples at all doses. This was a clear indication that the fish samples had been irradiated and that both methods of isolation (florisil and supercritical fluid extraction) were capable of qualitatively extracting this marker. Supercritical fluid extraction is proposed as an alternative extraction procedure to the florisil chromatography method currently in use and has the added advantage of a considerably shorter extraction time.

Iodine deficiency disorders among school children in upper Egypt: an epidemiologic study.

Iodine deficiency disorders (IDD) are the world's single most significant cause of preventable brain damage and mental retardation. Data regarding IDD in upper Egypt are scarce and even lacking. The aim of the present work was to study the prevalence of IDD and some potential risk factors in upper Egypt. Using a two-stage cluster sampling technique, 6750 school children aged 8-10 years were screened for IDD through clinical examination of the thyroid gland and determination of urinary iodine, from three governorates in upper Egypt, namely Al-Minya (population of 3.3 million), Assyut (population of 2.9 million), and Suhag (population of 3.1 million). Iodine was determined in samples of soil and drinking water. Overall, the prevalence rate of goitre was 34.6 per cent. The median urinary iodine level for children with goitre was 5.04 micrograms/dl compared to 14.81 micrograms/dl among children free of goitre. Multiple logistic regression analysis showed that certain groups of school children were much more likely to develop goitre. They included females (OR = 3.07, 95 per cent CI = 2.78-3.39), children in households where drinking water had an iodine content of less than 0.5 microgram/100 ml (OR = 3.44, 95 per cent CI = 3.09-3.89), and children living in places where soil content of iodine was less than 0.2 microgram/100 g (OR = 2.67, 95 per cent CI = 2.30-3.10). We conclude that IDD is a severe public health problem in upper Egypt. The present situation in upper Egypt necessitates an urgent intervention programme.

Pattern of electroencephalographic abnormalities in children with hydrocephalus: a study of 68 patients.

The pattern of electroencephalographic (EEG) abnormalities was studied in 68 patients (41 male, 27 female, age range 1 month to 17 years) with hydrocephalus. They all had standardized EEG recordings, which were read by the same electroencephalographer. In 48 children the EEG was performed after ventriculo-peritoneal shunting. The EEG abnormalities in the shunted group included slow waves in 26 patients [focal 2 (4.2%), generalized asynchronous 22 (45.8%), generalized synchronous 2 (4.2%)]; amplitude abnormalities in 2 (focal 1, generalized 1); epileptiform activity in 26 [partial 11 (22.9%), generalized 15 (31.3%)] and hypsarrhythmia in 4 (8.3%). Only 4 (8.3%) traces were normal, giving an overall percentage abnormality of 92%. In the unshunted group generalized asynchronous slow waves were found in 12 patients (60%), generalized amplitude abnormality in 1, focal epileptiform activity in 3 (15%), and generalized epileptiform activity in 6 (30%); 2 tracings in this group were normal, giving an overall percentage abnormality of 90%. Hydrocephalus in children, regardless of the cause, may be associated with generalized or focal EEG abnormalities. This may reflect the heterogeneity of the neural generator in the underlying disease process.

The effect of intermittent heating on some chemical parameters of refined oils used in Egypt. A public health nutrition concern.

As part of a public health campaign in Egypt, various chemical parameters of oil which are considered good indices in assessing the degree of thermal abuse, oxidation and overall quality (acid values, iodine values, peroxide values, etc.) were studied with respect to different frying oils. Ingestion of decomposition products formed as a results of thermal abuse and oxidation of frying oils are known to lead to a variety of symptoms and diseases (allergies, atherosclerosis, coronary heart disease). Results show that the oil most commonly used by street vendors in Egypt (blend of cotton seed and sunflower oil) is the least suitable for frying, while palm oil on the basis of the various chemical parameters studied, is the ideal choice. However, from the nutritional and public health stand point, the use of saturated oils is to be discouraged. Corn oil is therefore the next best choice from both the chemical and nutritional stand point, and is recommended for public use in a country in which deep-fried vegetable patties ('fallafel') forms the staple food item in the diet.

Implications of fructose in liver tumours of the Egyptian toad

Environmental factors play an important role in the etiology of several types of cancer; this discovery has led to a great deal of interest in the role of diet in cancer etiology. It is well known that some factories which produce jams and juices use fructose rather than glucose or sucrose to sweeten their products. This study demonstrates that fructose insignificantly enhances the incidence of liver tumours in Egyptian toads previously injected with 7,12-dimethylbenz [a]-anthracene

Electrophysiological findings in newly diagnosed non-insulin-dependent diabetics: A prospective study.

This study reports the electrophysiological findings in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) studied in the Neurodiagnostic Laboratory of the King Fahd Hospital of the University (KFHU), Al-Khobar, Saudi Arabia. Twenty-nine patients (22 males, 7 females, mean ages 47 and 37 years, respectively) were studied within four weeks of establishing the diagnosis. They were all given nerve conduction studies by the same examiner. Comparison was made with data from a group of 64 normal control subjects. In the study patients, the mean distal sensory peak latency in milliseconds (ms) +/- standard deviation (SD) was 3.5 +/- 0.41 ms in 35 median nerves, 3.2 +/- 0.72 ms in 35 ulnar nerves, 1.9 +/- 0.34 ms in 23 superficial radial nerves and 3.5 7plusmn; 0.61 in 36 sural nerves. The mean distal motor latency +/- SD was 4.6 +/- 0.95 ms in 39 median nerves, 3.5 +/- 0.58 ms in 38 ulnar nerves, 4.8 +/- 1.02 ms in 44 tibial nerves and 6.0 +/- 1.08 ms in 36 peroneal nerves. The electromyogram examination was performed on 24 patients and showed evidence of denervation and/or chronic reinnervation in seven (29%). The frequency of abnormalities in the studied peripheral nerves was 60% for median, 63% ulnar, 33% peroneal, 16% tibial and 8% sural.

Acute exacerbations of chronic bronchitis. Preventing treatment failures and early reinfection.

Although antimicrobial agents from a number of classes have been used with a good degree of clinical success for acute bacterial exacerbations of chronic bronchitis, the incidence of resistance by beta-lactamase-producing strains to certain penicillins and cephalosporins continues to increase and represents a growing clinical problem. There also have been reports of significant resistance by Streptococcus pneumoniae to tetracyclines and of treatment failures caused by this organism among patients receiving fluoroquinolones. The emergence of penicillin-resistant pneumococci in North America also is of concern. Although first-generation cephalosporins are no longer regarded as first-line therapy or optimal alternatives for acute exacerbations of chronic bronchitis, more recently developed agents of this class have better activity against the primary pathogens, and their efficacy and safety have been demonstrated in a number of clinical trials. Newer macrolide agents probably should be reserved for infections caused by atypical organisms.

The hemiplegic arm after stroke: measurement and recovery.

Seven clinical tests have been used to study the recovery of arm function in 92 patients over 2 years following their stroke. These tests are simple and quick, and can be used by any interested observer. They form a hierarchical scale that measures recovery. Statistically significant improvement is only seen in the first 3 months. Fifty-six patients initially had non-functional arms; eight made a "complete recovery" and 14 a partial recovery. The tests described are inadequate on their own because they are not sufficiently sensitive at the upper range of ability. While recovery of lost function does relate to the degree of initial neurological loss in the arm, it seems to be largely independent of the overall severity of the stroke.

Isometric contractions of normal and spastic human skeletal muscle.

Isometric contractile properties of human elbow flexor muscles were examined in 27 normal subjects (7 females and 20 males). Contractions of elbow flexors were elicited by application of electrical pulses to the biceps motor points. The tension development was recorded at the wrist with the elbow angle fixed at 90 degrees--100 degrees. The data for the time to peak and time to half relaxation of the twitch, the twitch tension-to-tetanus tension ratio, and the posttetanic twitch potentiation are reported. The contractile properties of spastic elbow flexor muscles from 7 subjects who had been hemiparetic for periods ranging from 4 months to 60 months were found to be similar to those of muscles in normal subjects and unaffected muscles in hemiparetic subjects.