Genetic study of congenital limb anomalies among Egyptian children

Objective: This study has been conducted to reveal genetically-determinedfactors that underlie the development of congenital limb anomalies amonga sample of Egyptian infants and children. These data might prove useful in taking preventive measures and/or providing proper counseling to concerned families.Subjects and Methods: The study comprised studying 140 (One hundred and forty) Egyptian children with congenital limb anomalies. They consisted of (98) males and (42) females ranging in age from 10 days to 18 years. All cases were selected from among patients attending the outpatient medical genetics clinic, faculty of medicine, Ain-Shams university, Cairo-Egypt. Enrolled cases were subjected to a list of investigations including complete history with pedigree construction, anthropometric measurements and full clinical examination. In addition, specific radio-imaging studies and laboratory investigations were done for cases necessitating further diagnostic workup. Results: The results of the study revealed that isolated limb anomalies were found in (55) patients representing (39.3%) of cases. The remaining eighty five (85) patients constituting (60.7%) of enrolled cases comprised two groups: those with limb defects as part of a well defined genetic syndrome (Syndromic limb defects) (76 patients - 54.3%) and those with limb defects as part of a chromosomal aberration syndrome (9 patients - 6.4%). Genealogical data of the study revealed that parental consanguinity is found in (47.3%) of cases with isolated limb defects, in (72.3%) of cases with syndromic limb defects and in (44.4%) of cases with limb defects due to chromosomal abnormalities. Valid history of prenatal drug intake by the mother was found in (43.6%) of cases with isolated limb defects, in (25%) of syndromic limb defects and in none of the cases with chromosomal abnormalities.Conclusions: Detailed analysis of data of the study drew useful  recommendations regarding many aspects like the possibility of prenatal diagnosis of most cases as well as the availability of many curative and/or palliative intervention measures for early detected and managed cases. Of prime importance, however, is the urgent need of alerting gynecologists and obstetricians taking care of pregnant women to the important role played by iatrogenic prescription of drugs during pregnancy in causation of many types of congenital limb anomalies. Cessation of this non-based evidence medical attitude is necessary and can result in a significant reduction in drug-induced congenital limb anomalies among newborns.Key Words: Limb anomalies, Egyptian children, consanguinity, chromosomal abnormalities

2-Hydroxypropyl-ß-Cyclodextrin Complex with Ketotifen Fumerate for Eye Drops Preparations

Ketotifen fumerate ophthalmic solution is an antihistaminic drug. The aim of this study was to develop a novel aqueous ketotifen eye drop formulation containin ketotifen/2-Hydroxypropyl-β-cyclodextrin complex, which has the ability to enhance the solubility of the drug at the physiological pH (7.4), consequently decreasing the irritation to the eye. Moreover, increaseing the fraction of the unionized drug leads to enhancing the permeability of the drug through the cornea. The stability constant was determined from phase-solubility diagrams and found to be higher with KF/HP-ß-CD complex (29.47 M−1) than KF/ß-CD complex (10.36 M−1). Differential scanning calorimetry (DSC), fourier transform-infrared (FT-IR) spectroscopy and X-ray analysis (X-ray) showed the formation and the physiochemical proporties of the complex. The effect of different additives including; antioxidants, isotonicity adjusting agents and preservatives on the stability of ketotifen fumerate solution were studied. Sodium ascorbate (0.1%w/v) showed a significant increase in the stability of the KF solutoion. Fluid thioglycolate medium and Tryptic Soy Broth were used as a medium to test of sterility of selected formulations to detect aerobic, anaerobic and fungal contamination and verified that no turbidity or surface growth was observed during the incubation period of all tested formulae. Finally, the chemical stability using the stability indicating HPLC assay showed that the stability of the selected formulation were significantly higher in comparison to that of a commercial product (Zaditen® eye drops Novartis Pharma-Egypt) (p>0.05). These results indicate that KF/HP-ß-CD eye drops formulation is a promising (formulation) resulting in enhancing the solability, stability and permeability of the drug.Keywords: Ketotifen Fumerate; 2-Hydroxypropyl-ß-cyclodextrin; Inclusion complex; Solubility; Stability

Schistosomiasis and Urinary Bladder Cancer in North Western Tanzania: A Retrospective Review of 185 Patients.

Worldwide, cancers of the urinary bladder are well known to be associated with environmental chemical carcinogens such as smoking and occupational exposure to polycyclic aromatic hydrocarbons. These cancers are typically transitional cell carcinoma (urothelial carcinoma). In areas where schistosomiasis is endemic there is a high incidence of squamous cell carcinoma of the urinary bladder. Schistosomiasis causes chronic granulomatous cystitis leading to squamous metaplasia of transitional epithelium, and subsequently development of squamous cell carcinoma. The western part of Tanzania on the shores of Lake Victoria is such an endemic area. This study was done to document the burden of urinary bladder cancer associated with schistosomiasis in this region. This was a descriptive retrospective study of histologically confirmed cases of urinary bladder cancer seen at the Department of Pathology Bugando Medical Centre (BMC) over a period of 10 years. Data were retrieved from the records of the Departments of Pathology, Medical Records and Surgery. Data were analyzed by the use of contingency tables. A total of 185 patients were diagnosed with cancer of the urinary bladder during the study period, where as 90 (48.6%) were males and 95 (51.4) were females. The mean age at diagnosis was 54.3 years. Squamous cell carcinoma was the most frequent histological type (55.1%), followed by conventional transitional cell carcinoma (40.5%). Eighty three of all cancer cases (44.9%) were found to have schistosomal eggs. Schistosomiasis was commonly associated with squamous cancers compared to non squamous cancers. Most of the cancers associated with schistosomiasis had invaded the muscularis propria of the urinary bladder at the time of diagnosis (p<0.001) and such cancers were frequent below 50 years of age with a significant statistical difference (p<0.001). Poorly differentiated tumors were more frequent in females than males with a significant statistical difference (p=0.006). The majority of urinary bladder cancers seen in the Lake Region were squamous cell carcinoma associated with schistosomiasis. These cancers showed an aggressive behavior and were commonly seen in the younger age groups. Effective control of schistosomiasis in this region should significantly reduce the burden of urinary bladder cancer

Intentions to use contraceptives in Pakistan: implications for behavior change campaigns

<p>Abstract</p> <p>Background</p> <p>Since 1990-91, traditional method use has increased at a faster rate in Pakistan than modern method use. The importance of hormonal methods or the IUD has diminished and that of traditional methods has increased in the method mix. There is a need to identify factors motivating and deterring the adoption of specific family planning methods among married men and women in Pakistan.</p> <p>Methods</p> <p>In addition to social and demographic characteristics of respondents, a representative household survey collected information on psychological correlates of family planning behavior from 1,788 non-pregnant wives and 1,805 husbands with not-pregnant wives. Males and females were from separate households. Principal components analysis was conducted to identify the underlying constructs that were important for each gender. Multinomial logistic regression analysis was conducted to determine the correlates of male and female intentions to use contraceptive methods.</p> <p>Results</p> <p>Amongst women, the perception that her in-laws support family planning use was the strongest determinant of her intentions to use contraceptive methods. A woman's belief in the importance of spacing children and her perception that a choice of methods and facilities with competent staff were available were also powerful drivers of her intentions to use contraceptive methods. The strongest obstacle to a woman's forming an intention to use contraceptive methods was her belief that family planning decisions were made by the husband and fertility was determined by God's will. Fears that family planning would harm a woman's womb lowered a woman's intentions to use methods requiring procedures, such as the IUD and female sterilization.</p> <p>The perception that a responsible, caring, husband uses family planning to improve the standard of living of his family and to protect his wife's health was the most important determinant of a man's intention to use condoms. A husband's lack of self-efficacy in being able to discuss family planning with his wife was the strongest driver of the intention to use withdrawal. A man's fear that contraceptives would make a woman sterile and harm her womb lowered his intention to use modern contraceptive methods.</p> <p>Conclusions</p> <p>These findings highlight the importance of having secondary target audiences such as mothers-in-law and husbands in family planning behavior change campaigns implemented in Pakistan. Campaigns that stress the importance of child spacing are likely to have an impact. Client perceptions of the quality of care are important determinants of intentions to use contraceptive methods in Pakistan. Client concerns that the IUD and sterilization procedures might harm a woman's womb and cause sterility should be addressed. The findings suggest that there is a need to assess the actual quality of service delivery in Pakistan.</p

Low Spigelian hernia in a 6-year-old boy presenting as an incarcerated inguinal hernia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Lower Spigelian hernia is a very rare entity. The clinical findings are similar to those of inguinal hernias and in many cases may be misdiagnosed. In the literature, only a few references to this entity have been reported in children. To the best of our knowledge, this is the first case report of a lower Spigelian hernia in a child who presented with an acute painful scrotum.</p> <p>Case presentation</p> <p>We discuss the case of a 6-year-old Greek boy who presented to our emergency department complaining of severe pain in the left inguinal area and scrotum. The acute painful swelling started suddenly, without any obvious cause. The initial diagnosis was incarcerated inguinal hernia which was reduced with difficulty. Five days later, the patient still experienced mild pain during palpation and he was operated on. During the operation, a large lower Spigelian hernia was revealed and reconstructed.</p> <p>Conclusion</p> <p>Although Spigelian hernias are rare in children and difficult to diagnose, physicians should be aware of them and include them in the differential diagnosis.</p

CKD classification based on estimated GFR over three years and subsequent cardiac and mortality outcomes: a cohort study

<p>Abstract</p> <p>Background</p> <p>It is unknown whether defining chronic kidney disease (CKD) based on one versus two estimated glomerular filtration rate (eGFR) assessments changes the prognostic importance of reduced eGFR in a community-based population.</p> <p>Methods</p> <p>Participants in the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study were classified into 4 groups based on two eGFR assessments separated by 35.3 ± 2.5 months: sustained eGFR < 60 mL/min per 1.73 m²(1 mL/sec per 1.73 m²); eGFR increase (change from below to above 60); eGFR decline (change from above to below 60); and eGFR persistently ≥60. Outcomes assessed in stratified multivariable Cox models included cardiac events and a composite of cardiac events, stroke, and mortality.</p> <p>Results</p> <p>There were 891 (4.9%) participants with sustained eGFR < 60, 278 (1.5%) with eGFR increase, 972 (5.4%) with eGFR decline, and 15,925 (88.2%) with sustained eGFR > 60. Participants with eGFR sustained < 60 were at highest risk of cardiac and composite events [HR = 1.38 (1.15, 1.65) and 1.58 (1.41, 1.77)], respectively, followed by eGFR decline [HR = 1.20 (1.00, 1.45) and 1.32 (1.17, 1.49)]. Individuals with eGFR increase trended toward increased cardiac risk [HR = 1.25 (0.88, 1.77)] and did not significantly differ from eGFR decline for any outcome. Results were similar when estimating GFR with the CKD-EPI equation.</p> <p>Conclusion</p> <p>Individuals with persistently reduced eGFR are at highest risk of cardiovascular outcomes and mortality, while individuals with an eGFR < 60 mL/min per 1.73 m²at any time are at intermediate risk. Use of even a single measurement of eGFR to classify CKD in a community population appears to have prognostic value.</p

Agronomic Management of Indigenous Mycorrhizas

Many of the advantages conferred to plants by arbuscular mycorrhiza (AM) are associated to the ability of AM plants to explore a greater volume of soil through the extraradical mycelium. Sieverding (1991) estimates that for each centimetre of colonized root there is an increase of 15 cm3 on the volume of soil explored, this value can increase to 200 cm3 depending on the circumstances. Due to the enhancement of the volume of soil explored and the ability of the extraradical mycelium to absorb and translocate nutrients to the plant, one of the most obvious and important advantages resulting from mycorrhization is the uptake of nutrients. Among of which the ones that have immobilized forms in soil, such as P, assume particular significance. Besides this, many other benefits are recognized for AM plants (Gupta et al, 2000): water stress alleviation (Augé, 2004; Cho et al, 2006), protection from root pathogens (Graham, 2001), tolerance to toxic heavy metals and phytoremediation (Audet and Charest, 2006; Göhre and Paszkowski, 2006), tolerance to adverse conditions such as very high or low temperature, high salinity (Sannazzaro et al, 2006), high or low pH (Yano and Takaki, 2005) or better performance during transplantation shock (Subhan et al, 1998). The extraradical hyphae also stabilize soil aggregates by both enmeshing soil particles (Miller e Jastrow, 1992) and producing a glycoprotein, golmalin, which may act as a glue-like substance to adhere soil particles together (Wright and Upadhyaya, 1998). Despite the ubiquous distribution of mycorrhizal fungi (Smith and Read, 2000) and only a relative specificity between host plants and fungal isolates (McGonigle and Fitter, 1990), the obligate nature of the symbiosis implies the establishment of a plant propagation system, either under greenhouse conditions or in vitro laboratory propagation. These techniques result in high inoculum production costs, which still remains a serious problem since they are not competitive with production costs of phosphorus fertilizer. Even if farmers understand the significance of sustainable agricultural systems, the reduction of phosphorus inputs by using AM fungal inocula alone cannot be justified except, perhaps, in the case of high value crops (Saioto and Marumoto, 2002). Nurseries, high income horticulture farmers and no-agricultural application such as rehabilitation of degraded or devegetated landscapes are examples of areas where the use of commercial inoculum is current. Another serious problem is quality of commercial available products concerning guarantee of phatogene free content, storage conditions, most effective application methods and what types to use. Besides the information provided by suppliers about its inoculum can be deceiving, as from the usually referred total counts, only a fraction may be effective for a particular plant or in specific soil conditions. Gianinazzi and Vosátka (2004) assume that progress should be made towards registration procedures that stimulate the development of the mycorrhizal industry. Some on-farm inoculum production and application methods have been studied, allowing farmers to produce locally adapted isolates and generate a taxonomically diverse inoculum (Mohandas et al, 2004; Douds et al, 2005). However the inocula produced this way are not readily processed for mechanical application to the fields, being an obstacle to the utilization in large scale agriculture, especially row crops, moreover it would represent an additional mechanical operation with the corresponding economic and soil compaction costs. It is well recognized that inoculation of AM fungi has a potential significance in not only sustainable crop production, but also environmental conservation. However, the status quo of inoculation is far from practical technology that can be widely used in the field. Together a further basic understanding of the biology and diversity of AM fungi is needed (Abbott at al, 1995; Saito and Marumoto, 2002). Advances in ecology during the past decade have led to a much more detailed understanding of the potential negative consequences of species introductions and the potential for negative ecological consequences of invasions by mycorrhizal fungi is poorly understood. Schwartz et al, (2006) recommend that a careful assessment documenting the need for inoculation, and the likelihood of success, should be conducted prior to inoculation because inoculations are not universally beneficial. Agricultural practices such as crop rotation, tillage, weed control and fertilizer apllication all produce changes in the chemical, physical and biological soil variables and affect the ecological niches available for occupancy by the soil biota, influencing in different ways the symbiosis performance and consequently the inoculum development, shaping changes and upset balance of native populations. The molecular biology tools developed in the latest years have been very important for our perception of these changes, ensuing awareness of management choice implications in AM development. In this context, for extensive farming systems and regarding environmental and economic costs, the identification of agronomic management practices that allow controlled manipulation of the fungal community and capitalization of AM mutualistic effect making use of local inoculum, seem to be a wise option for mycorrhiza promotion and development of sustainable crop production

Cubic exact solutions for the estimation of pairwise haplotype frequencies: implications for linkage disequilibrium analyses and a web tool 'CubeX'

<p>Abstract</p> <p>Background</p> <p>The frequency of a haplotype comprising one allele at each of two loci can be expressed as a cubic equation (the 'Hill equation'), the solution of which gives that frequency. Most haplotype and linkage disequilibrium analysis programs use iteration-based algorithms which substitute an estimate of haplotype frequency into the equation, producing a new estimate which is repeatedly fed back into the equation until the values converge to a maximum likelihood estimate (expectation-maximisation).</p> <p>Results</p> <p>We present a program, "CubeX", which calculates the biologically possible exact solution(s) and provides estimated haplotype frequencies, D', r²and <it>χ</it>²values for each. CubeX provides a "complete" analysis of haplotype frequencies and linkage disequilibrium for a pair of biallelic markers under situations where sampling variation and genotyping errors distort sample Hardy-Weinberg equilibrium, potentially causing more than one biologically possible solution. We also present an analysis of simulations and real data using the algebraically exact solution, which indicates that under perfect sample Hardy-Weinberg equilibrium there is only one biologically possible solution, but that under other conditions there may be more.</p> <p>Conclusion</p> <p>Our analyses demonstrate that lower allele frequencies, lower sample numbers, population stratification and a possible |D'| value of 1 are particularly susceptible to distortion of sample Hardy-Weinberg equilibrium, which has significant implications for calculation of linkage disequilibrium in small sample sizes (eg HapMap) and rarer alleles (eg paucimorphisms, q < 0.05) that may have particular disease relevance and require improved approaches for meaningful evaluation.</p

Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort

Aims: Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients.// Methods and results: BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02–2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28–2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract).// Conclusion: Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS.// Clinical Trial Registration: The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106