An eco-friendly direct spectrofluorimetric method for the determination of irreversible tyrosine kinase inhibitors, neratinib and pelitinib: application to stability studies.

A new rapid and simple stability-indicating spectrofluorimetric method has been developed for the determination of two irreversible tyrosine kinase inhibitors (TKIs), neratinib (NER) and pelitinib (PEL). The method is based upon measurement of the native fluorescence intensity of both drugs at λex 270 nm in aqueous borate buffer solutions (pH 10.5). The fluorescence intensity recorded at 545 nm (NER) and 465 nm (PEL) were rectilinear over the concentration range of 0.1-10 µg/mL for both drugs with a high correlation coefficient (r > 0.999). The proposed method provided low limits of detection and of quantitation of 0.07, 0.11 µg/mL (NER) and 0.02, 0.05 µg/mL (PEL), respectively. The method was successfully applied for the determination of NER and PEL in bulk powder. The proposed methods were fully validated as per the International Conference on Harmonisation (ICH) guidelines. The application of the method was extended to stability studies of both NER and PEL under different forced-degradation conditions (acidic-induced, base-induced, oxidative, wet heat, and photolytic degradation). Moreover, the kinetics of the base-induced and oxidative degradation of both drugs was investigated and the pseudo-first-order rate constants and half-lives were estimated at different temperatures. Also, an Arrhenius plot was applied to predict the stability behaviour of the two drugs at room temperature. Copyright © 2016 John Wiley & Sons, Ltd.

Laparoscopic herniotomy in children: prospective assessment of tertiary center experience in a developing country.

PURPOSE: We aimed to assess prospectively the feasibility and outcome of laparoscopic herniotomy (LH) in children in a tertiary center with limited resources. METHODS: Fifty-six children with unilateral pediatric inguinal hernia (PIH) were treated for an 18-month period. All cases were subjected to LH in a way similar to the classic open technique following exploration of the contralateral patent processus vaginalis (CPPV) without ligation of the sac. Exclusion criteria included prematurity, age <6 months, irreducible or recurrent hernia, and cases with internal ring diameter >2 cm. Operative findings, postoperative results, and complications were assessed. RESULTS: We have 56 cases presented with unilateral PIH, and they are aged between 6 months and 15 years. Thirty-two presented with Rt hernia including 12 associated with CPPV and 24 cases Lt hernia with 10 associated with CPPV. Two cases showed adhesions and 2 cases showed direct defects that were repaired in the same session. Hydrocele of the hernia sac was reported once. In the total of 78 hernias, the mean operative time was 20.5 min in unilateral cases and 42.5 min in bilateral cases. No conversion was reported. Postoperative pain lasts for a mean time of 11.2 h. Patients regained peristalsis by a mean of 7 h. Two cases developed wound infection and were treated conservatively. No case of recurrence, testicular atrophy, or hydrocele was reported in the mean follow-up period of 20.5 months. CONCLUSIONS: Laparoscopic herniotomy is feasible and safe for PIH. It provides a superior tool to diagnose CPPV or rare hernias that can be managed in the same session with minimal postoperative complications reported even in developing countries. Laparoscopic herniotomy is proved to be beneficial for PIH since it provides an excellent view on the cord structures, and they can be guarded well during the procedure. Larger studies and longer follow-up are needed to support our encouraging results.

Use of the TIP principle for the repair of non-glanular recurrent post hypospadias urethrocutaneous mega fistula.

INTRODUCTION: The most significant complication after hypospadias repair is urethrocutaneous fistula. Repair is even more difficult if the fistula is large. Use of the tubularized incised plate (TIP) procedure for hypospadias repair has greatly increased. However, use of the TIP procedure for the repair of recurrent mega fistula has not been previously described. The aim of this study is to present the results of a modified TIP procedure for the repair of recurrent mega fistula occurring after hypospadias repair. METHODS: All cases of recurrent penile mega fistula after hypospadias repair presenting to our institution between 2002 and 2008 were included in our study. Cases with coronal or glanular fistulae were excluded. Diameters of these large fistulae were > or =0.5 cm. Repair was done a minimum of 6 months after the last repair. After complete dissection of the fistula, the excision was extended a further 2 mm all around the edge in a circumferential manner. A dorsal slit in the penile urethra was made based on the TIP procedure; the urethroplasty was completed using interrupted sutures. Second layer coverage was done and the skin was closed. RESULTS: A total of 11 boys (median age at surgery: 8 years) who developed mega fistula after hypospadias repair were included in the study. The patients had undergone previous attempts at repair, with the number of previous attempts ranging between 1 and 9 times. The last repair was done 6-48 months before surgery (median: 16 months). Fistulae diameters were between 5 and 13 mm (median: 9 mm). All patients underwent the same procedure, with a follow-up period of between 6 and 72 months (median: 33 months). In 7 cases 2 layers were used to cover the urethroplasty, while in 4 cases used only one layer. There were no intraoperative complications. Two cases suffered superficial infection postoperatively, one of whom developed a small fistula (1/11). CONCLUSIONS: The advantages of a procedure based on the TIP principle for the treatment of recurrent penile mega fistula are numerous. The procedure is easy to perform and can be successfully used to treat recurrent urethrocutaneous fistula in carefully selected cases. Our recurrence rate of 9% is acceptable. Use of a modified TIP procedure for the repair of mega fistula or partial penile disruption is feasible. More cases are needed to support our initial findings of this new use of the TIP procedure in hypospadias surgery.

Laparoscopically assisted gradual controlled traction on the testicular vessels: a new concept in the management of abdominal testis. A preliminary report.

INTRODUCTION: The study was performed to assess the benefit of gradual traction for the management of abdominal testis by lengthening instead of dividing the testicular vessels. PATIENTS AND METHODS: After approval by the ethical committee of the Faculty of Medicine of the University of Alexandria, and after parents signed a detailed informed consent, ten children with unilateral intra-abdominal testis were operated upon laparoscopically. The gubernaculum and the lower pole of the testis were attached with a 2/0 Prolene stitch which exited above the contralateral anterior superior spine. Gradual traction on the tension stitch was achieved over 14 days. A laparoscopy was performed after 14 days to check the new position of the testis and to locate the testis intrascrotally. Follow-up was done after 6-12 months to check the position and size of the testis, and color Doppler was performed to check the vascularity. RESULTS: Ages ranged between 1 and 5 years (mean 2.3 yrs). Three testes were right-sided and 7 left-sided. In one case slipping of the traction suture occurred and the patient had conversion to a conventional Fowler-Stephens technique. Nine cases showed adequate elongation after traction and were successfully positioned in the scrotum. Follow-up was 6-12 months (mean 8.7 months). On follow-up, 9 testes were found intrascrotally with a normal size and consistency. Doppler study showed normal vascularity, both venous and arterial. CONCLUSION: This preliminary study showed that the technique of gradual controlled traction on the testicular vessels is very promising to achieve elongation and medialization of the testicular vessels instead of division. The measurable elongation allowed intrascrotal placement of the testis without tension. The technique cannot yet be recommended for routine use. Further comparative studies with a larger patient series are mandatory before the technique can be generally recommended.

Integrated waste management for rural development in Egypt.

Rural areas generate a large amount of plant and animal residues that can be recycled and utilized instead of relocation and/or burning. This will lead to increasing the benefits from agricultural sector in rural communities and ensuring a better environment. To increase the economic output and environmental benefits of recycling agricultural residues, integrated system should be considered, e.g., energy--compost-recycled water system; composting--co-composting system; food-feed compost system, ensilage of crop residues. The present work was a pilot study for optimizing integrated systems for bioconversion agricultural residues completed by establishing a Training Center for Recycling Agricultural Residues (TCRAR) thereby ensuring the dissemination of the technical, environmental, and socioeconomic aspects to farmers, live stock producers, extensions service staff, and private sector. Three integrated subsystems for bioconversion of agricultural residues were developed. They were based on (i) energy--manure-recycled water system, (ii) composting and co-composting system, and (iii) food-feed/compost system.

Double half-cone flap umbilicoplasty: a new technique for the proboscoid umbilical hernia in children.

OBJECTIVE: Although many techniques have been described for reconstruction of the protruding umbilicus in children with umbilical hernia, we present a simple new technique for umbilicoplasty. METHODS: Ten children (six males and four females) with umbilical hernias and protruding skin were operated upon. Operative description consists of amputation of the protruding umbilical skin, leaving two unequal half-cones, a short cephalic half-cone (0.5 cm) and a long caudal half-cone (1 cm). These two half-cones are fashioned, closed, and inverted to constitute the new umbilicus following a classic hernia repair. RESULTS: The early results were excellent in all cases with no infection and no ischaemic changes encountered in the skin of the reconstructed umbilicus. Follow-up periods between 6 and 18 months revealed a cosmetically pleasing shape of the umbilicus. Only one case developed hypertrophy of the resulting scar. CONCLUSION: We present our initial experience with the new technique. This new technique provides a good solution for reconstruction of the protruding umbilical skin. Our double half-cone flap umbilicoplasty technique is easy to learn and to perform.

Remodeling of pulmonary arteries in human congenital diaphragmatic hernia with or without extracorporeal membrane oxygenation.

PURPOSE: The aim of this study was to describe in detail the perinatal developmental profile of the pulmonary vasculature in congenital diaphragmatic hernia (CDH) and to examine the potential beneficial effects of extracorporeal membrane oxygenation (ECMO) on the vascular morphology. Additionally the authors aimed to identify the differences in pulmonary vascular morphology among CDH cases according to the primary cause of death: either extreme lung hypoplasia (LH) or persistent pulmonary hypertension (PPH). METHODS: The authors studied autopsy sections from 30 high-risk CDH cases with respect to the pulmonary arteries in relation to gestational age (GA) and ECMO treatment. They were grouped into CDH-I: 20 cases with GA greater than 34 weeks who were not subjected to ECMO and CDH-II: 10 cases with GA greater than 34 weeks, who were subjected to ECMO for an average time of 237 hours. Five age-matched neonates who died from placental insufficiency or birth asphyxia without evidence of lung hypoplasia served as controls (CON). Medial and adventitial thicknesses of pulmonary arteries were measured in lung sections stained with Elastic van Gieson by 2 investigators blinded for the clinical data. Immunohistological staining with anti-alpha-smooth muscle actin (alpha-SMA) was performed to confirm the precise location of the arterial media before morphometry. CDH cases were subgrouped and compared according to the primary cause of death. Unpaired Student t test was used for statistics, with significant P value < or =.05. RESULTS: In CDH newborns, a significant increase in medial, adventitial, and total wall thickness was found in pulmonary arteries with an external diameter of less than 200 microm as compared with age-matched controls (P<.004, .0001, and .0009, respectively). ECMO-treated CDH newborns showed a significantly thinner arterial adventitia than CDH patients who did not receive this treatment (P<.0001), approaching normal values. However, the medial thickness remained increased. Morphometrically, no significant differences in CDH cases between patients dying of PPH or severe LH could be determined. CONCLUSIONS: (1) In CDH, there is failure of the normal arterial remodeling processes occurring in the perinatal period. (2) Pulmonary vascular morphology in CDH does not differ between the groups with lung hypoplasia or persistent pulmonary hypertension as primary cause of death. (3) Adventitial thinning of these arteries might be one of the mechanisms by which ECMO alters PPH in CDH cases.

Spondylothoracic dysplasia with diaphragmatic defect: a case report with literature review.

Spondylothoracic dysplasia (Jarcho-Levin syndrome) is a syndrome of unknown etiology. We describe a new case with diaphragmatic eventration. Literature review for cases of Jarcho-Levin syndrome with diaphragmatic defects, which were six cases, revealed that renal affection increased when diaphragmatic defects associate the syndrome with pulmonary hypoplasia. Thus, the subgroup of spondylothoracic dysplasia with diaphragmatic defect is a more severe subgroup of the syndrome rather than the other forms of this syndrome. Relating the described anomalies in this case and that of the literature cases to the known embryological basis may point to a pivotal developmental link between lung, kidney and diaphragm, possibly the posterior mesenchyme.

Expression patterns of heat shock proteins in lungs of neonates with congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is associated in many cases with pulmonary hypertension. Currently, extracorporeal membrane oxygenation (ECMO) is one of the possible modalities of treatment of pulmonary hypertension and prevention of parenchymal lung injury in neonates with CDH. HYPOTHESIS: Molecular stress is present in the lungs of neonates with CDH. To test this hypothesis, we investigate the expression pattern of stress genes (heat shock proteins [HSPs] 27 and 70) in lungs of patients with CDH who have pulmonary hypertension, and evaluate the influence of ECMO on the expression levels of these genes to understand the underlying molecular mechanisms. DESIGN: Paraffin-embedded lung autopsy specimens from patients with CDH and lung hypoplasia who either did or did not receive ECMO treatment and age-matched controls were immunostained by means of monoclonal antihuman antibodies against HSP 70 and HSP 27, with the streptavidin-biotin complex method. SETTING: Level III academic children's hospital. MAIN OUTCOME MEASURES: Expression levels of both HSP 27 and HSP 70 were semiquantitatively evaluated in bronchial epithelium, as well as in medial smooth muscle cells (SMCs) and endothelium of large and small pulmonary arteries, by means of a score ranging from 0 to 4. Statistical analysis of the data was performed with the nonparametric Mann-Whitney test, with significant probability value at P < or = .05. RESULTS: For HSP 70, the most pronounced immunoreactivity was observed in the bronchial epithelium, followed by the medial SMCs of small arteries (of external diameter < 200 microm). The overall expression was significantly higher in patients with CDH than controls in bronchi as well as in pulmonary arteries. For HSP 27, intense expression was found in medial SMCs, followed by the bronchial epithelium in controls, with significantly increased expression in medial SMCs of large and small arteries in patients with CDH. Treatment with ECMO was associated with significantly reduced expression levels of HSP 70 in medial SMCs of both large and small arteries, whereas HSP 27 expression levels were decreased only in small arteries. In addition, the expression levels of both HSPs were significantly lower in endothelium of small arteries. CONCLUSIONS: Increased expression of HSPs in CDH points to a condition of pulmonary stress. This pulmonary stress appears to be partially ameliorated by ECMO treatment. This may point to one of the mechanisms by which ECMO alleviates pulmonary hypertension associated with CDH.

Impaired structural remodelling of pulmonary arteries in newborns with congenital diaphragmatic hernia: a histological study of 29 cases.

Congenital diaphragmatic hernia (CDH) is associated in many cases with lung hypoplasia and pulmonary hypertension (PH). The pathogenetic mechanisms underlying the pulmonary hypertension in CDH are not completely understood. In order to alleviate the pulmonary hypertension, new therapeutic modalities have been introduced including extracorporeal membrane oxygenation (ECMO). This paper reports a study of the histology of the lungs of 29 CDH autopsy cases, with special attention to the pulmonary arteries, and relating the findings to gestational age and ECMO treatment. Formalin-fixed and paraffin-embedded specimens were stained with haematoxylin and eosin (H&E) and elastic van Gieson (EvG) stains, followed by morphometric measurements of the arterial media and adventitia. As expected, there was a significant decrease in adventitial percentage and total wall thicknesses of small pulmonary arteries with an external diameter less than or equal to 150 microm in term control newborns compared with pre-term controls (p=0.0004 and 0.05). In CDH newborns, all the measured values of the arterial wall remained significantly higher. The increase of adventitial thickness also affected the supernumerary arteries in CDH neonates. CDH newborns subjected to ECMO treatment showed a significantly thinner arterial adventitia than CDH cases who did not receive ECMO (p=0.0001), the former approaching normal values. These results indicate that in CDH, there is failure of the normal arterial remodelling processes occurring in the perinatal period. The adventitial thickening, which has been reported previously in term CDH patients only, was related in the present study to differences in gestational ages. This appears to be partially reversed by ECMO treatment, thus constituting one of the mechanisms by which ECMO treatment aids in alleviating the associated PH in CDH newborns.

Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension.

BACKGROUND: Pulmonary hypoplasia accompanied by pulmonary hypertension resistant to treatment is an important feature of congenital diaphragmatic hernia (CDH). The pathogenesis of the pulmonary vascular abnormalities in CDH remains to be elucidated at the molecular level. Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, is known to play a role in pulmonary angiogenesis and vascular remodelling but there are no data on VEGF expression in patients with CDH. METHODS: Necroscopic lung specimens from 21 patients with CDH with lung hypoplasia and from seven age matched control newborn infants without lung hypoplasia were processed for immunohistochemical analysis using affinity purified anti-human VEGF antibodies. All the cases of CDH had pulmonary hypoplasia, indicated by a lung/body weight index of 200 microm) and small (<200 microm) pulmonary arteries, the most intense staining being in the medial smooth muscle cells of the small pulmonary arteries. Endothelial cells were positive for VEGF staining in patients with CDH but not in controls. CONCLUSIONS: This is the first study of VEGF expression in newborn infants with CDH. Increased levels of VEGF, especially in the small, pressure regulating pulmonary arteries, point to a potential role in vascular remodelling. This may reflect an unsuccessful attempt by the developing fetus to increase the pulmonary vascular bed in the hypoplastic lungs to alleviate the associated pulmonary hypertension.

Long-term evaluation of modified lateral anorectal myomectomy for low-segment Hirschsprung disease.

OBJECTIVES: To provide a simple myomectomy technique for low-segment Hirschsprung disease and evaluate the efficacy of the new modification. DESIGN: Case series of 19 patients followed up for 12 to 56 months (mean, 39.1 months). SETTING: Tanta University Hospital, Tanta, Egypt. PARTICIPANTS: Nineteen patients aged 4 months to 10 years complaining of chronic constipation, with radiological and clinical data suggestive of low-segment Hirschsprung disease proven by histological examination. INTERVENTION: Modified lateral anorectal myomectomy. MAIN OUTCOME MEASURES: Clinical and radiological improvement measured by postoperative barium enema, bowel habits, and patient's relief of symptoms. RESULTS: Seventeen of 19 patients improved clinically and 13 showed radiological improvement 3 years postoperatively. There was poor response in 2 patients, who were subjected to further Soave procedures. CONCLUSION: Modified lateral anorectal myomectomy is an effective and technically simple procedure in patients suspected of having low-segment Hirschsprung disease.

Effect of new anticancer methanesulfonates on different biochemical parameters of mouse liver.

The comparative effect to two chemically related new synthesized anticancer drugs namely 3,3'-(methylimino) di(l-propanol)dimethanesulfonate(ester)diphenyl disulfonate, No. 838 D (NSC, 140-115) and 3,3' iminodi-l-propanol dimethanesulfonate(ester)p-toluene disulfonate, No. 864 T (NSC, 140-117), on liver DNA, RNA, lipids and glucose-6-phosphatase, after single 100 mg i.p. injection was studied. Both drugs significantly reduced DNA, RNA and total lipid content on day one and two after administration. Normal levels were regained on day three. Both drugs did not cause a decrease in glucose-6-phosphatase activity level, on the contrary, the enzyme was significantly elevated on day three after administration. The present results demonstrate that these drugs induce no severe or permanent damage to hepatic cells in the administered dose.

Activity of enzymes in organic carbon-amended soils treated with varying levels of salts.

The effect of varying concentrations of either NaCl or Na2CO3 (0, 10, 20, and 25 meq/100 g soil) and organic carbon (0 and 2% starch) on the activity of dehydrogenase, urease, and phosphatase (nuclease) was studied in incubated samples of alluvial clay and calcareous sandy loam soils. Moisture content was kept at 60% W.H.C. The level of 10 meq/100 g soil of either sodium chloride or sodium carbonate was stimulatory for the activity of the three enzymes studied in both soils tested. The increasing concentrations of Na2CO3 showed greater changes in the enzymatic activity than the corresponding concentrations of NaCl in both soils. Application of starch reduced the inhibitory effect of the high levels of such salts on the enzymatic activities in both soils, except for phosphatase which was depressed by Na2SO3 in starch-amended soil samples. The calcareous soil responded to the starch addition less than the alluvial soil.

Enzymatic activities during incubation of remoistened soil samples stored for different periods.

Periodical measurements for the activities of dehydrogenase, urease, and phosphatase (nuclease) were undertaken during incubation of remoistened alluvial clay and calcareous sandy loam soil samples stored (air-dried) over ten months. All enzyme activities showed fluctuating values within both incubation time and storage period. Dehydrogenase activity tended to increase by storage of samples of both soils. Urease revealed, generally, decreasing values, whilst phosphatase showed no definite trend with the lapse of storage period.

Evaluation of some biological tests as parameters for microbial activities in soils. II. Field investigations.

Investigations were designed to study the effect of certain factors on the microbial activities in soil. The parameters, used as an index of the microbial activities, were total bacterial counts, dehydrogenase activity, oxidation of organic carbon, and CO2 evolved/7 days. Bahteem Farm clay soil was examined for determining the effects of depth, type of fertilization, and crop rotation on the microbial activities. It appears that the microbial activities, as indicated by the tested parameters, were more pronounced in the surface 15 cm-layer than in the subsurface layer (15-30 cm). Results of all the parameters tested showed markedly higher increases with farmyard manure than with nitrogenous fertilizer and in the control, without significant differences between the latter two. Moreover, the time of sampling had no effect on the results obtained for all parameters. Different types of rotations did not exert significant variation in total bacterial counts, though more than one crop per year increased the organic carbon content of soil and mostly the dehydrogenase activity, whereas the evolution of CO2 tended to decrease. At Gabal el-Asfar Farm, the effect of irrigation with sewage effluent, for long periods, on the microbial activities of sandy soil was investigated. Sewage water stimulated the total bacteria, raised the dehydrogenase activity, the organic carbon, and the production of CO2. In North El Tahreer and Mariut Sectors, the effect of both the type and age of cultivation on the microbial activities in the calcareous soils were examined. Cultivation raised the figures of all the tested parameters progressively with time of cultivation. It was also noticed that crops exerted more beneficial effects on microbial activities than orchards, and the dehydrogenase test was the most reliable parameter to reveal this fact.

Biological activities during ripening of composts.

Three investigations were carried out. The first determined the relationships between dehydrogenase acitivty throughout the course of composting wheat straw and the changes in both organic carbon and total nitrogen. The second investigation tested the validity of the first investigation results. The third dealt with the effect of the degree of ripening of a compost, expressed by age and C/N ratio, on its dehydrogenase activity, and production of CO2. The results revealed continual decreases in the organic carbon, coincident with increases in total N and dehydrogenase activity. Noticeable chemical and biological changes occurred in the first and third month. Levels of dehydrogenase were highest in rice straw and lowest in cotton stalk compost, while the wheat straw compost occupied an intermediate position. Aging of the compost resulted in increases in the dehydrogenase figures and decreases in the amounts of CO2 produced.