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The diagnosis of epilepsy depends upon a number of factors, particularly detailed and accurate seizure history, or semiology. Other diagnostic data, consisting of electroencephalography, video-monitoring of the seizures, and magnetic resonance imaging, are important in any comprehensive epilepsy program, particularly with respect to lateralizing and localizing the seizure focus, if such a focus exists, and with respect to determining the type of seizure or seizure syndrome. The aim of this review is to present a survey of important semiologic characteristics of various seizures that provide the historian with observations, which help to lateralize and localize epileptic zones. Clinical semiology is the starting point of understanding a seizure disorder and making the diagnosis of epilepsy. While it may not provide unequivocal evidence of localization of the epileptic focus, nevertheless it usually directs subsequent investigations, whose concordance is necessary for the ultimate localization.

Many physicians consider examining the nervous system as one of the most difficult parts of the physical examination. Difficult and poorly cooperative children remain the most challenging group to examine accurately and completely. In this situation, the physician becomes less confident about the neurological findings and clinical evaluation. Several factors are predictive of difficult behavior during the evaluation, including anxiety when meeting unfamiliar people, short time to adjust to the medical situation, previous hospitalization, fear of injections, and parental anxiety. Limited neurological literature addresses the issues relating to the examination of difficult and poorly cooperative children. In this review, some practical tips and techniques are presented that can be used to improve the likelihood of obtaining accurate information about the neurological status of young and difficult children. Certainly, repeated examinations and experience play an important role; however, solid knowledge, strong communication skills, accurate observational skills, and use of proper techniques are crucial for eliciting and interpreting neurological signs in difficult children. Finally, a patient and empathetic physician and supportive guiding parents are needed for a successful neurological assessment.

Acute spinal subdural hematoma is a somewhat rare pathology. Its severity comes from the constitution of an acute spinal cord compression. In many cases MRI is useful for the differential diagnosis with the epidural hematoma. A 79-year-old patient was referred for emergency neurosurgery for acute spinal cord compression. The vascular risk in this patient was significant: hypertension, oral anticoagulants. Clinically, acute non-traumatic subdural spinal hematoma was suspected. The spinal cord MRI was in favor of the diagnosis which was confirmed intraoperatively. The surgical procedure revealed an extensive hematoma which infiltrated the spinal cord. The diagnosis of nontraumatic subdural spinal hematoma may be difficult in some cases and correctly established only during the surgical procedure. In comparison with reports in the literature, we discuss the underlying mechanisms of this hematoma. Spinal subdural haematoma must be considered in patients taking anticoagulant therapy or with a coagulation disorder who present signs of acute spinal cord compression. MRI sagittal T1 and T2-weighted images are adequate and reliable for diagnosis of spinal subdural hematoma. Prompt surgical evacuation of this hematoma is crucial.

Seizures are the most common pediatric neurological emergency.1,2 Adequate education is important for their proper identification, intervention, and management.3,4 Parents’ behavior during an acute seizure is influenced by their knowledge and experience. Although parents generally feel informed about epilepsy and its management, many still have significant misconceptions and misinformation.5 Such misconceptions should be identified and corrected for optimal care and management. In a recent Saudi study,6 although most parents stated that they know what to do in an acute seizure situation, up to 14% performed unnecessary procedures, such as sprinkling water to the face, shaking, or carrying the child around. This behavior was less likely if the parents achieved college or university education. More inappropriate or potentially harmful procedures related to mythical concepts were reported from other developing countries, such as forcing liquids by mouth, pressure over body to restrain convulsive movements, or putting some object to force the teeth open.7 Our objectives were to study maternal knowledge -of and behavior during acute seizures, and identify correlating and contributing factors to their negative behavior and actions. These may include their personal and social experiences, as well as, their socio-economic and educational levels. These issues have received limited study in our region. We hypothesize that many families in Saudi Arabia are not properly informed on what to do during an acute seizure. Some are misinformed from unreliable sources leading to negative management decisions and practices.

The aim of this study was to compare the immediate versus the delayed application of photobiomodulation (PBM) therapy following odontectomy of horizontally impacted mandibular third molars, and assess which application method is more effective at reducing postoperative complications.Surgical removal of horizontally impacted mandibular third molars is a common surgical procedure, usually associated with postoperative complications such as pain, swelling, and trismus. Several attempts have been made to minimize these complications. One such method is the use of PBM therapy.Eighty patients with horizontally impacted mandibular third molars with no inferior alveolar canal approximation were recruited for this study. They were divided into two groups. The immediate group received PBM therapy immediately after surgery and on the 3rd day postoperatively. Subjects in the delayed group received PBM therapy on the 2nd and 4th days postoperatively. All subjects received 2 min of treatment using a 4 W laser beam, during which 171 J were delivered via a 2.8 cm(2) spot size.Clinical and statistical results showed a significant reduction in pain, trismus, and swelling in the immediate PBM therapy group compared with the delayed PBM therapy group.Immediate PBM therapy is more effective than delayed PBM therapy in minimizing the complications associated with mandibular third molar removal surgery.

Adding to its well-known roles in locomotion and calcium balance, the skeleton has recently been appreciated as a true endocrine organ. Bone remodeling, a highly dynamic process, requires synchronized activities and crosstalk between bone cells. Discovery and characterization of the Wnt/β catenin pathway in bone formation, FGF23 regulation of phosphate homeostasis and osteocalcin in energy and glucose homeostasis have reframed our view of the skeleton from simply a target tissue of the endocrine system to an endocrine tissue itself. This comprehensive review provides an overview of these complex pathways, their application to human bone disorders and implications for developing diagnostic and therapeutic targets.

Midgut volvulus is a complication of malrotation of bowel and mesenteric malfixation. In contrast, primary volvulus of the small bowel is a distinctly different and rare entity characterized by torsion of the entire small bowel with normal mesenteric fixation. To present the clinical and imaging findings in four infants with primary small bowel volvulus and normal bowel fixation in order to improve awareness of this entity among clinicians and radiologists and to discuss the potential etiologies of this entity to distinguish it from other causes of small bowel volvulus. A retrospective review of imaging studies (two ultrasounds and four upper gastrointestinal series) in four infants (three full-term and one premature) from three institutions with surgically proven volvulus of the entire small bowel and normal bowel fixation were reviewed by three board-certified pediatric radiologists and correlated with clinical and surgical reports when available. The infants presented during the first week to 6 months of life and were acutely ill. The upper gastrointestinal series showed complete duodenal obstruction with beaking in one and partial duodenal obstruction in three. All studies were interpreted as highly suspicious for malrotation and midgut volvulus. Emergent laparotomy demonstrated primary small bowel volvulus with normal mesenteric fixation in all infants. The base of the small bowel mesentery was described by the operating surgeon as smaller than normal in one infant (case 3). There was no mesenteric defect or other abnormality predisposing to volvulus in the other three. In both infants who had abdominal US, a retroperitoneal position of the third portion of the duodenum was demonstrated. All infants survived. One infant required resection of the necrotic small bowel and currently has short gut syndrome, one has malabsorption and two were lost to follow-up. Primary small bowel volvulus with normal fixation is indistinguishable from malrotation with midgut volvulus in the acutely ill infant or child. Radiographic diagnosis can be difficult in patients with intermittent or incomplete small bowel volvulus without malrotation. In these patients, neither an upper gastrointestinal series demonstrating a normal position of the duodenojejunal junction nor the sonographic demonstration of a retromesenteric third portion of the duodenum excludes the diagnosis. In young infants, the clinical and imaging findings may mimic necrotizing enterocolitis. Sonography may be useful to evaluate the bowel for signs of bowel wall compromise or a whirlpool sign.

The population hospitalised in psychiatry seems more exposed to traumatic events than the French general population, with particularly more sexual aggressions. The aim of this study is to describe the population hospitalised in psychiatry and more precisely the traumatic history of these patients, their comorbidities (mental diseases and addictions), and socio economical level. This descriptive, cross sectional and retrospective study took place in the Crisis Center in the University Hospital in Martinique (French West Indies), from February to July 2013. A socio-demographic information, the Mini International Neuropsychiatric Interview 5.0, the Trauma History Questionnaire and the Impact Events Scale-Revised were realised with 49 of the 143 patients admitted during this period (34.3%). In this population, we found a mean of 6.5 (standart-deviation=4.2) different types of traumatic event, with 38.8% patients reporting a natural disaster, and 38.8% declaring at least one sexual aggression. In the 25 patients suffering from post-traumatic stress disorder, 66.7% underwent a sexual aggression, significatively during childhood (before 10 years old, P=0.01), and during adolescence (between 10 to 18 years old, P=0.01). These results underline the importance of a systematic screening of the traumatic profile: the characteristics of the traumatic events and its clinical impact.

Parathyroid hormone (PTH) secretion is regulated by a complex interplay of circulating minerals and hormones that include extracellular calcium (via the calcium-sensing receptor, CaSR), plasma phosphate, 1,25-dihydroxyvitamin D (1,25(OH) 2 D), and fibroblast growth factor 23 (FGF23). The most common causes of secondary hyperparathyroidism are renal disease and vitamin D deficiency. Although less common, other conditions that cause secondary hyperparathyroidism include disorders of calcium balance (deficiency, malabsorption, and excess excretion), disorders associated with FGF23 excess, persistent parathyroid disease after renal transplant, specific disorders of acid–base balance, and ingestion of certain medications.

Contexte : Les meres d'enfants presentant une epilepsie refractaire au traitement eprouvent un haut niveau de stress et presentent plus de problemes emotifs. La fatigue peut affecter leur productivite, leurs interactions sociales et leur capacite a prendre soin adequatement de leurs enfants. Cette etude avait pour objectif d'examiner la relation entre l'epilepsie refractaire de l'enfance et la fatigue maternelle et d'explorer les facteurs qui y contribuent. Methodes : Soixante-quatre meres d'enfants atteints d'epilepsie refractaire ont ete identifiees consecutivement de facon prospective. Les meres d'enfants atteints de maladies degeneratives ou metaboliques ou de maladies potentiellement fatales comme les tumeurs cerebrales etaient exclues. La fatigue etait mesuree au moyen d'un questionnaire standardise de 11 items qui a ete revalide dans la population de langue arabe. Resultats : Les meres etaient âgees de 24 a 45 ans (âge moyen de 34 ans et l'âge moyen de leurs enfants epileptiques etait de 1 a 15 ans (âge moyen de 6,7 ans). La plupart des enfants (64%) etaient epileptiques depuis plus de 2 ans, prenaient plus d'un medicament antiepileptique (72%) et avaient des crises quotidiennes (47%). Trente-quatre (54%) des enfants avaient des deficits moteurs et 83% avaient un retard mental qui etait severe chez 41%. Vingt-huit (44%) des meres etaient fatiguees. Les facteurs associes a une fatigue maternelle plus severe etaient les suivants : un enfant de moins de 2 ans (p = 0,01), une epilepsie cryptogenique (p = 0,03) et des deficits moteurs severes (p = 0,004). Les facteurs associes a une fatigue moindre etaient l'activite physique reguliere (p = 0,006), l'absence de retard mental (p = 0,01), le controle des crises (p = 0,05), l'utilisation d'un seul antiepileptique (p = 0,002), des visites peu frequentes au service d'urgences (p = 0,005) et l'absence d'hospitalisation recente (p = 0,005). Conclusions : Les meres des enfants atteints d'epilepsie refractaire eprouvent de plus en plus de fatigue. Plusieurs facteurs qui y sont correles ont ete identifies, surtout en rapport avec le controle des crises et le handicap mental et physique. Parmi les strategies pour gerer le probleme citons une education adequate, le controle des crises, l'activite physique reguliere, le soutien social et la consultation en psychologie.

Consumptive hypothyroidism is characterized by excessive inactivation of thyroid hormone by type 3 iodothyronine deiodinase (D3). Previously this rare syndrome was described in association with massive hemangiomas in children and in a single case of a hemangioendothelioma in an adult. Here we report the first case of consumptive hypothyroidism from a nonvascular tumor in a patient who required supraphysiologic doses of levothyroxine prior to the resection of a large malignant solitary fibrous tumor. The tumor expressed D3 message, protein and exhibited functional D3 enzymatic activity. The clinical presentation of this patient expands the differential diagnosis of hypothyroidism, adds to the growing list of paraneoplastic syndromes that impact the endocrine system, and extends the spectrum of tumor types associated with consumptive hypothyroidism.

Objectives Burnout is a common work-related syndrome consisting of emotional exhaustion, depersonalization and diminished feelings of personal accomplishment. Burnout influences the performance and efficiency of the healthcare professionals and therefore the quality of the care provided. This study aims to assess the burnout rates and potential determinants in pediatrics. Methods A cross-sectional, descriptive study involving physicians practicing pediatrics in the Jeddah area of Saudi Arabia was conducted utilizing the Maslach Burnout Inventory in addition to questions regarding work-related and lifestyle-related factors. Results One hundred and thirty pediatricians (55% females) were included with age ranging between 25 and 45 years (mean: 30). Most (46%) were consultants and 54% practiced in a university based setting. Burnout scores were abnormal in 107 (82%) and in 45 (34%) the syndrome was severe. Males were more likely to reach a severe burnout category compared to females (40% vs. 31%; p=0.012). Academic pediatricians working in a university setting were much more likely to experience severe burnout compared to their counterparts working in other hospitals (50% vs. 19%; p=0.0005). Consultants were also more likely to experience severe burnout compared to residents and assistants (46% vs. 27%; p=0.03). Conclusion At least one third of practicing pediatricians suffer from burnout syndrome. Specific strategies should be developed and implemented to limit and prevent professional burnout.

Cerebral cavernous malformations (CCM) are hamartomatous vascular malformations characterized by abnormally enlarged capillary cavities without intervening brain parenchyma. They cause seizures and focal neurological deficits due to cerebral hemorrhages. CCM loci have already been assigned to chromosomes 7q (CCM1), 7p (CCM2), and 3q (CCM3) and have been identified in 40%, 20%, and 40%, respectively, of families with CCM. Loss-of-function mutations have been identified in CCM1/KRIT1, the sole CCM gene identified to date. We report here the identification of MGC4607 as the CCM2 gene. We first reduced the size of the CCM2 interval from 22 cM to 7.5 cM by genetic linkage analysis. We then hypothesized that large deletions might be involved in the disorder, as already reported in other hamartomatous conditions, such as tuberous sclerosis or neurofibromatosis. We performed a high-density microsatellite genotyping of this 7.5-cM interval to search for putative null alleles in 30 unrelated families, and we identified, in 2 unrelated families, null alleles that were the result of deletions within a 350-kb interval flanked by markers D7S478 and D7S621. Additional microsatellite and single-nucleotide polymorphism genotyping showed that these two distinct deletions overlapped and that both of the two deleted the first exon of MGC4607, a known gene of unknown function. In both families, one of the two MGC4607 transcripts was not detected. We then identified eight additional point mutations within MGC4607 in eight of the remaining families. One of them led to the alteration of the initiation codon and five of them to a premature termination codon, including one nonsense, one frameshift, and three splice-site mutations. All these mutations cosegregated with the disease in the families and were not observed in 192 control chromosomes. MGC4607 is so far unrelated to any known gene family. Its implication in CCMs strongly suggests that it is a new player in vascular morphogenesis.

Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome of osteomalacia due to phosphate wasting. The phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMTMCT) is an extremely rare, distinctive tumor that is frequently associated with OO. Despite its association with OO, many PMTMCTs go unrecognized because they are erroneously diagnosed as other mesenchymal tumors. Expression of fibroblast growth factor-23 (FGF-23), a recently described protein putatively implicated in renal tubular phosphate loss, has been shown in a small number of mesenchymal tumors with known OO. The clinicopathological features of 32 mesenchymal tumors either with known OO (29) or with features suggestive of PMTMCT (3) were studied. Immunohistochemistry for cytokeratin, S-100, actin, desmin, CD34, and FGF-23 was performed. The patients (13 male, 19 female) ranged from 9 to 80 years in age (median 53 years). A long history of OO was common. The cases had been originally diagnosed as PMTMCT (15), hemangiopericytoma (HPC) (3), osteosarcoma (3), giant cell tumor (2), and other (9). The tumors occurred in a variety of soft tissue (21) and bone sites (11) and ranged from 1.7 to 14 cm. Twenty-four cases were classic PMTMCT with low cellularity, myxoid change, bland spindled cells, distinctive "grungy" calcified matrix, fat, HPC-like vessels, microcysts, hemorrhage, osteoclasts, and an incomplete rim of membranous ossification. Four of these benign-appearing PMTMCTs contained osteoid-like matrix. Three other PMTMCTs were hypercellular and cytologically atypical and were considered malignant. The 3 cases without known OO were histologically identical to the typical PMTMCT. Four cases did not resemble PMTMCT: 2 sinonasal HPC, 1 conventional HPC, and 1 sclerosing osteosarcoma. Three cases expressed actin; all other markers were negative. Expression of FGF-23 was seen in 17 of 21 cases by immunohistochemistry and in 2 of 2 cases by RT-PCR. Follow-up (25 cases, 6-348 months) indicated the following: 21 alive with no evidence of disease and with normal serum chemistry, 4 alive with disease (1 malignant PMTMCT with lung metastases). We conclude that most cases of mesenchymal tumor-associated OO, both in the present series and in the reported literature, are due to PMTMCT. Improved recognition of their histologic spectrum, including the presence of bone or osteoid-like matrix in otherwise typical cases and the existence of malignant forms, should allow distinction from other mesenchymal tumors. Recognition of PMTMCT is critical, as complete resection cures intractable OO. Immunohistochemistry and RT-PCR for FGF-23 confirm the role of this protein in PMTMCT-associated OO.

Pediatric neurology is considered a relatively new and evolving subspecialty. In Saudi Arabia, neurologic disorders in children are common, and the demand for trained pediatric neurologists is strong. The aim was to study the perception of the pediatric neurology specialty among practicing generalists and their referral practices. Attendees of a symposium on pediatric epilepsy comprehensive review for the generalist were included. A structured 25-item questionnaire was designed to examine their demographics, training, practice, and referral patterns. One hundred nineteen participants attended the symposium, and 90 (76%) questionnaires were returned. Attendees' ages were 22 to 70 years (mean 32 years), with 65.5% female physicians. There were 32% consultants, 51% trainees, and 17% students. Most physicians (67%) were practicing general pediatrics. Only 36% received a structured pediatric neurology rotation during training. Children with neurologic complaints constituted 28.5% of those seen in their practice, and they referred 32.5% of them to pediatric neurology. Only 32% were moderately or highly confident in making the diagnosis or providing the appropriate treatment. Those who received a structured pediatric neurology rotation felt more comfortable in their management ( P = .03). Many physicians (38.5%) had no direct access to a pediatric neurologist for referrals. To conclude, pediatric neurologic disorders are common in daily practice. Most generalists did not receive a structured neurology rotation during their training and were not highly confident in diagnosing and treating these children. Given the limited number of pediatric neurologists, I highly recommend that generalists receive appropriate neurologic training. ( J Child Neurol 2004;19:1—5).

Systems of linear inequalities are important tools to formulate optimization problems. However, the feasibility of the whole system was often presumed true in most models. Even if an infeasible system could be detected, it is in general not easy to tell which part of the system caused it. This motivates the study of continuous linear inequalities, given no information whether it is feasible or not, what is the largest possible portion of the system that can be remained in consistency? We first propose a bisection-based algorithm which comes with an auxiliary program to answer the question. For further accelerating the algorithm, several novel concepts, one called “constraint weighting” and the other called “shooting technique”, are introduced to explore intrinsic problem structures. This new scheme eventually replaces the bisection method and its validity can be justified via a solid probabilistic analysis. Numerical examples and applications to fuzzy inequalities are reported to illustrate the robustness of our algorithm.

Tumors associated with osteomalacia elaborate the novel factor(s), phosphatonin(s), which causes phosphaturia and hypophosphatemia by cAMP-independent pathways. We show that secreted frizzled-related protein-4 (sFRP-4), a protein highly expressed in such tumors, is a circulating phosphaturic factor that antagonizes renal Wnt-signaling. In cultured opossum renal epithelial cells, sFRP-4 specifically inhibited sodium-dependent phosphate transport. Infusions of sFRP-4 in normal rats over 2 hours specifically increased renal fractional excretion of inorganic phosphate (FEPi) from 14% ± 2% to 34% ± 5% (mean ± SEM, P < 0.01). Urinary cAMP and calcium excretion were unchanged. In thyro-parathyroidectomized rats, sFRP-4 increased FEPi from 0.7% ± 0.2% to 3.8% ± 1.2% (P < 0.05), demonstrating that sFRP-4 inhibits renal inorganic phosphate reabsorption by PTH-independent mechanisms. Administration of sFRP-4 to intact rats over 8 hours increased FEPi, decreased serum phosphate (1.95 ± 0.1 to 1.53 ± 0.09 mmol/l, P < 0.05) but did not alter serum 1α, 25-dihydroxyvitamin D, renal 25-hydroxyvitamin D 1α-hydroxylase cytochrome P450, and sodium-phosphate cotransporter mRNA concentrations. Infusion of sFRP-4 antagonizes Wnt action as demonstrated by reduced renal β-catenin and increased phosphorylated β-catenin concentrations. The sFRP-4 is detectable in normal human serum and in the serum of a patient with tumor-induced osteomalacia. Thus, sFRP-4 displays phosphatonin-like properties, because it is a circulating protein that promotes phosphaturia and hypophosphatemia and blunts compensatory increases in 1α, 25-dihydroxyvitamin D.

Albright hereditary osteodystrophy (AHO) is a genetic disorder caused by heterozygous inactivating mutations in GNAS1, the gene encoding the -chain of Gs, and is associated with short stature, obesity, brachydactyly, and sc ossifications. AHO patients with GNAS1 mutations on maternally inherited alleles also manifest resistance to multiple hormones (e.g. PTH, TSH, LH, FSH), a variant termed pseudohypoparathyroidism (PHP) type 1a, due to paternal imprinting of Gs transcripts in specific tissues. Recent evidence has shown that Gs transcripts are also imprinted in the pituitary somatotrophs that secrete GH. Because this imprinting could influence GHRH-dependent stimulation of somatotrophs, we hypothesized that maternally inherited GNAS1 mutations would impair GH secretion. We studied GH status in 13 subjects with PHP type 1a. GH responses to arginine/L-dopa and arginine/ GHRH were deficient in nine subjects, all of whom were obese and had low serum concentrations of IGF-I. By contrast, none of the four GH-sufficient subjects were obese, and all had normal IGF-I levels. Our data indicate that GH deficiency is common (69%) in PHP type 1a and may contribute to the obesity and short stature typical of AHO. We propose that GH status be evaluated in all patients with PHP type 1a. (J Clin Endocrinol Metab 88: 4059 – 4069, 2003)

Although the molecular basis of pseudohypoparathyroidism type 1b (PHP type 1b) remains unknown, a defect in imprinting at the GNAS1 locus has been suggested by the consistent finding of paternal-specific patterns of DNA methylation on maternally inherited GNAS1 alleles. To characterize the relationship between the genetic and epigenetic defects in PHP type 1b, we analyzed allelic expression and methylation of CpG islands within exon 1A of GNAS1 in patients with sporadic PHP type 1b and in affected and unaffected individuals from five multigenerational kindreds with PHP type 1b. All subjects with resistance to parathyroid hormone (PTH) showed loss of methylation of the exon 1A region on the maternal GNAS1 allele and/or biallelic expression of exon 1A–containing transcripts, consistent with an imprinting defect. Paternal transmission of the disease-associated haplotype was associated with normal patterns of GNAS1 methylation and PTH responsiveness. We found that affected and unaffected siblings in one kindred had inherited the same GNAS1 allele from their affected mother, evidence for dissociation between the genetic and epigenetic GNAS1 defects. The absence of the epigenetic defect in subjects who have inherited a defective maternal GNAS1 allele suggests that the genetic mutation may be incompletely penetrant, and it indicates that the epigenetic defect, not the genetic mutation, leads to renal resistance to PTH in PHP type 1b.

Pseudohypoparathyroidism (PHP) is characterized by biochemical hypoparathyroidism with elevated parathyroid hormone levels owing to reduced target tissue responsiveness to parathyroid hormone. Patients with PHP la have somatic defects termed Albright's hereditary osteodystrophy (AHO) and exhibit resistance to additional hormones because of heterozygous mutations in the GNAS1 gene that lead to a generalized deficiency of the a subunit of Gs, the heterotrimeric G protein that couples receptors to adenylyl cyclase. By contrast, patients with PHP 1b lack AHO and have selective parathyroid hormone (PTH) resistance, presumably because of an imprinting defect that impairs expression of G(s)alpha in the proximal renal tubule. Although an epigenetic defect in GNAS1 has been identified in subjects with PHP1b, the genetic defect is unknown. To define the genetic defect in PHP 1b, we performed a genome-wide linkage analysis in five multi-generational PHP lb families. Of the 408 polymorphic microsatellite markers examined, markers located on chromosome 20q13.3, the region containing GNAS1, demonstrated linkage to PHP lb. Fine-mapping and multipoint linkage analysis of this region demonstrated linkage to a 5.7-cM region between 907rep2 and the telomere. Haplotype analysis established that affected individuals shared a 5-cM region including part of the GNAS1 gene to the telomere. Our data confirm that PHP1b is linked to a region that includes GNAS1, and further refine the locus, although the primary genetic mutation(s) that causes defective imprinting of GNAS1 remains undefined.

This study is based on a retrospective analysis of 150 cases of tympanoplasty and ossicular chain reconstruction as a one-stage procedure. It was conducted at the Federal Government Services Hospital, Islamabad from 1983 to 1999. Temporalis fascia was used for myringoplasty and a sculptured autologous incus to bridge the malleus to stapes head and malleus to footplate gap. These interpositions have produced stable ossicular assemblies and provided satisfactory post-operative hearing gains. One hundred and twenty-six (84 per cent) patients achieved a healed tympanic membrane three months post-operatively. One year post-operatively, 121 (81 per cent) patients had an intact tympanic membrane and at five years 119 (79 per cent) had an intact tympanic membrane. The success rate was based on an intact tympanic membrane and an air-bone gapof less than 30 dB one-year post-operation. Accordingly, the overall success rate was 80 per cent (120 cases). Hearing gains in cases with an absent stapes arch were poorer than in cases with an intact arch. Early (one to three months) post-operative complications included tympanic membrane perforation, lateralization of the graft and persistence of infection. Late (one to five years) complications included the appearance of an anterior perforation and retraction and thinning of the tympanic membrane.

Oncogenic osteomalacia (OOM) is associated with primitive mesenchymal tumors that secrete phosphaturic factors resulting in low serum concentrations of phosphate and calcitriol, phosphaturia, and defective bone mineralization. To identify overexpressed genes in these tumors, we compared gene expression profiles of tumors resected from patients with OOM and histologically similar control tumors using serial analysis of gene expression (SAGE). Three hundred and sixty-four genes were expressed at least twofold greater in OOM tumors compared with control tumors. A subset of 67 highly expressed genes underwent validation with an extended set of OOM and control tumors using array analysis or reverse-transcription polymerase chain reaction (RT-PCR). Ten of these validated genes were consistently overexpressed in all OOM tumors relative to control tumors. Strikingly, genes with roles in bone matrix formation, mineral ion transport, and bone mineralization were highly expressed in the OOM tumors.

This report summarizes several aspects of protein kinase A (PKA) signaling and its involvement in health and disease. It follows the discovery that PRKAR1A, the gene that codes for the relatively abundant regulatory subunit type 1A of protein kinase A, is the tumor suppressor gene responsible for the multiple endocrine neoplasia syndrome known as "Carney complex." Although cyclic AMP (cAMP)-dependent signaling has already been found to be involved in the pathogenesis of other genetic conditions predisposing to tumor development, this is the first time that PKA itself was directly involved in tumorigenesis and, perhaps, carcinogenesis in an inherited disease.

Objectives: To review the available techniques and procedures for management of parotid and submandibular sialoliths with special emphasis on the efficacy and safety of the most commonly used combination of techniques; namely, sialendoscopy with conservative surgical removal of the stone. Methods: A systematic search of the English literature using MEDLINE, EMBASE, and the Cochrane library databases were conducted at the Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia. Articles between the years 2004 and 2013 were selected on the basis of preset inclusion criteria. Then, they were reviewed against a checklist to assess the evidence of efficacy of therapy or prevention and analyzed for pertinent data. Results: Eleven articles met the inclusion criteria and were reviewed and analyzed. The success rate of sialendoscopy combined with minor surgical removal of parotid and submandibular sialoliths ranges from 69-100%. Conclusion: Sialendoscopy combined with a minor surgical extraction of parotid and submandibular sialoliths is safe and efficacious.

To examine public awareness and attitudes toward epilepsy in Riyadh, the capital city of Saudi Arabia.A focused 10-item questionnaire was designed to survey public awareness and attitudes toward epilepsy. Personal interviews were conducted randomly by one author in preselected public places in Riyadh, Saudi Arabia during March and April 2011.Seven hundred and forty-nine interviews were completed during the study period. Most participants (77.4%) had prior knowledge of epilepsy, and 52% believed that epilepsy is an organic disease. This correlated with their educational level, as those with higher levels of education were more likely to link epilepsy to organic causes (p=0.008). However, 15% also linked epilepsy to evil spirit possession, and up to 37% preferred spiritual rituals and religious healing to medical treatments. Although most respondents (61%) would accept an epileptic patient in a regular job, 71% (particularly males) reported reservations in marrying someone with epilepsy (p=0.001).The awareness and attitudes of the Saudi public toward epilepsy are showing some improvement. However, it is still thought to be linked to evil spirit possession by some, and spiritual rituals and religious healing are commonly believed to be effective treatments. Targeted areas for focused education were identified.

Metabolic syndrome is a common complication encountered in children surviving acute lymphoblastic leukaemia (ALL). Affected patients develop obesity, insulin resistance, hypertension, and hyperlipidemia. Metabolic syndrome is a consequence of multiple factors, particularly hormonal imbalance induced by various ALL treatments. This review aims to evaluate the risk factors and mechanisms leading to the development of metabolic syndrome. Further research is needed to improve our understanding of the mechanisms leading to insulin resistance and the associated endothelial and adipose tissue dysfunction. Future studies should also examine other possible contributing factors, such as environmental and genetic factors. Understanding these factors will help in guiding modifications of the current ALL treatment protocols in order to prevent the development of this syndrome and hence improve the quality of life of ALL survivors. Until this is achieved, clinicians should continue to identify patients at risk early and use a therapeutic approach that combines dietary restrictions and enhanced physical activity.

Unprotected left main disease which till recently was considered a class III indication for PCI has been accepted as a IIb indication in the last updated AHA/ACC guidelines. Now world over , UPLM stenting is being increasingly taken up , especially after the entry of drug eluting stents in the coronary interventional arena. The distal left main disease is considered the technically most challenging. We present here a case of distal left main disease with critical ostial LAD and LCX disease, successfully managed with stenting via the double barrel technique. J Med Sci 2010;13(1):25-27

Background:Infantile gratification phenomena are self-stimulatory behaviors that are often misdiagnosed as epilepsy. Although the prognosis is thought to be benign, limited long-term follow-up studies exist. This was the objective of our study in addition to exploring the risks of future developmental, behavioral, or neurological abnormalities.Methods:Series of consecutive infants with gratification phenomena were identified both retrospectively and prospectively over an eight year period from a single pediatric neurology service. The diagnosis was based on descriptive history, review of videotaped events, lack of neurological or developmental abnormalities, and normal routine electroencephalogram.Results:Nineteen infants were followed for 3-11 years (mean 7.1). Their ages ranged between 4-13 months (mean 7) with 79% females. The diagnosis was not reached by the referring physician and 74% were misdiagnosed as epilepsy or movement disorder. The episodes recurred with variable frequency with gradual reduction in number and increase in length of attack-free periods with advancing age. Complete remission was noted in all patients by age 1-3 years (mean 1.9). However, 4 children (21%) developed features of attention deficit hyperactivity disorders (ADHD) on long-term follow up. In this group, the gratification phenomena appeared at a younger age with higher attack frequency.Conclusions:Gratification phenomena in infants are benign and self-limited, often spontaneously disappearing by two years of age. A correlation with future ADHD was found; however, larger prospective studies are needed to further examine this possible association.

Sleep disorders are common in children with mental retardation and neurologic disorders. Melatonin, a recently developed natural compound, has been used successfully in sleep disorders. I report my experience with melatonin in an open, prospective trial to treat circadian rhythm sleep disorder in handicapped children. The sleep disorder had been present for at least 6 months and had not responded to at least one hypnotic drug. The therapeutic response was recorded according to the average number of hours asleep per 24 hours, average number of awakening per night, average number of nights with delayed sleep onset, and average number of nights with early morning arousals. Ten consecutive children (four males, six females; age range = 1-11 years, mean 5.4) were included. Nine children had documented mental retardation that was severe in six (67%). Most had epilepsy and visual impairment (70%). All children were monitored for 4-12 months (mean 7.5 months) after the initiation of 3-mg bedtime melatonin. Most (80%) had a dramatic response to melatonin. No side effects were reported. Melatonin is a well-tolerated, safe, relatively inexpensive, and effective drug, with minimal side effects, for the treatment of severe circadian rhythm sleep disorder in handicapped children. Wider use of this drug is recommended.

This study surveyed the selection practices of group leaders. The study explored methods of selection, variables used to make selection decisions, and the types of selection errors that leaders have experienced. The results suggest that group leaders use clinical judgment to make selection decisions and endorse using some specific variables in selection, and that selection errors can have a detrimental effect on the selected member, the group, and the leader. Suggestions on ways that these selection errors might have been prevented are also reported.

Pseudohypoparathyroidism 1b (PHP 1b) is characterized by specific resistance of target tissues to PTH, but no mutations in the PTH/PTH-related peptide (PTHrP) receptor gene have been identified. To investigate the basis for defective PTH signaling, we used polymorphic markers in or near the genes encoding PTH and its receptors to perform linkage analysis between these loci and PHP 1b. Two multiplex PHP 1b families (families M and K) were informative for an intragenic polymorphism in exon 13 of the PTH/PTHrP receptor gene detected by PCR amplification and resolved by denaturing gradient gel electrophoresis. Linkage analysis revealed discordance of the PTH/PTHrP receptor with PHP1b. One PHP 1b kindred (family M) was informative for a intragenic polymorphism in exon 3 of the PTH gene detected by PCR amplification and resolved by denaturing gradient gel electrophoresis. The PTH gene polymorphism segregation was discordant with PHP 1b. Probands from each family had normal PTH genes by direct sequence analysis. In three PHP 1b kindreds, we analyzed simple sequence polymorphisms in three microsatellite markers flanking the PTH type 2 receptor locus located at 2q33. Linkage analysis demonstrated no linkage. In conclusion, neither the PTH gene nor the PTH receptor genes (type 1 and 2) are linked to PHP 1b.

The effects of long-term endurance exercise training, body composition, and cardiovascular fitness (VO2max) on the activity of adipose tissue lipoprotein lipase (AT-LPL) and lipoprotein lipids were examined in 66 healthy age-matched middle-aged and older men (mean +/- SE, 61 +/- 1 years). We compared subcutaneous abdominal (ABD) and gluteal (GLT) heparin-elutable AT-LPL activity in 19 master athletes (VO2max40 mL/kg/min) and 20 lean sedentary men (VO2max40 mL/kg/min) versus 27 obese sedentary men (VO2max40 mL/kg/min; body fat27%). Fasting insulin and leptin levels were similar in master athletes and lean sedentary men, but were lower than in obese sedentary men. There were no differences in fasting values for total cholesterol or low-density lipoprotein cholesterol (LDL-C) among the groups, but master athletes had lower triglyceride (TG) values (P.05) and higher high-density lipoprotein cholesterol (HDL-C) and HDL2-C (P.05) than obese and lean sedentary men. There were no regional (ABD v GLT) differences in the activity of AT-LPL in these groups, but obese sedentary men had higher levels of ABD AT-LPL (2.1 +/- 0.3 nmol/10(6) cells x min) than lean sedentary men (0.8 +/- 0.2) and master athletes (0.5 +/- 0.1, P = .01). Similar results were observed for GLT AT-LPL. Both ABD and GLT AT-LPL activity correlated positively with percent body fat (r = .46 to .54, P.001), fasting insulin (r = .37 to .45, P.001), and leptin (r = .61 to .65, P.0001), but not with VO2max. In stepwise multiple regression analysis, leptin was the main independent predictor of ABD (R2 = .43, P.0001) and GLT (R2 = .40, P.0001) AT-LPL activity. Plasma TG correlated positively (r = .32, P.01) and HDL-C correlated negatively (r = -.32, P = .02) with ABD AT-LPL activity, but these relationships were not significant after controlling for percent body fat or leptin. The results of this study indicate that in healthy middle-aged and older men, the major determinants of AT-LPL activity are obesity and its major associated hormones, leptin and insulin, not cardiovascular fitness, and also suggest that the higher HDL-C levels observed in endurance-trained men are not associated with increased AT-LPL activity.

This monograph presents computational techniques and numerical analysis to study conservation laws under uncertainty using the stochastic Galerkin formulation. With the continual growth of computer power, these methods are becoming increasingly popular as an alternative to more classical sampling-based techniques. The approach described in the text takes advantage of stochastic Galerkin projections applied to the original conservation laws to produce a large system of modified partial differential equations, the solutions to which directly provide a full statistical characterization of the effect of uncertainties. Polynomial Chaos Methods of Hyperbolic Partial Differential Equations focuses on the analysis of stochastic Galerkin systems obtained for linear and non-linear convection-diffusion equations and for a systems of conservation laws; a detailed well-posedness and accuracy analysis is presented to enable the design of robust and stable numerical methods. The exposition is restricted to one spatial dimension and one uncertain parameter as its extension is conceptually straightforward. The numerical methods designed guarantee that the solutions to the uncertainty quantification systems will converge as the mesh size goes to zero. Examples from computational fluid dynamics are presented together with numerical methods suitable for the problem at hand: stable high-order finite-difference methods based on summation-by-parts operators for smooth problems, and robust shock-capturing methods for highly nonlinear problems. Academics and graduate students interested in computational fluid dynamics and uncertainty quantification will find this book of interest. Readers are expected to be familiar with the fundamentals of numerical analysis. Some background in stochastic methods is useful but not necessary.

Background: The Oxfordshire Community Stroke Project clinical classification of ischemic stroke syndromes has been shown to be predictive of important clinical outcomes. In this study, we examined the correlation between this classification system and infarct topography on computed tomography (CT) of the brain. Method: A cohort of consecutive cases of acute ischemic stroke admitted to an acute stroke service during the 3-year period ending December 31, 1996 were identified from a prospective stroke registry. Brain scans were reviewed by a single neuroradiologist without knowledge of the clinical features. Results: There were 418 patients with acute ischemic stroke who met the study admission criteria. Forty patients were excluded, 20 (5%) did not have a CT scan during the admission, and 20 scans were not available for review. In 239 of 378 patients (63%), the brain scan revealed the lesion responsible for the clinical syndrome. In patients with positive scans, the positive predictive values of the clinical subtypes were: 86% (95% confidence interval, 78–94) for the total anterior territory stroke syndrome, 96% (92–100) for the partial anterior territory stroke syndrome, 99% (97–100) for the lacunar stroke syndrome, and 100% for the posterior circulation stroke syndrome. Conclusion: The Oxfordshire Community Stroke Project classification of ischemic stroke syndromes usefully predicts infarct topography on CT scan.

Patients with Niemann-Pick type D have been traced to a single Acadian ancester in Nova Scotia. The objective of this study was to describe the clinical course. A cohort of children with Niemann-Pick type D was identified by chart review. Some children were seen and a telephone interview with the remaining parents was conducted. Twenty children with Niemann-Pick type D were identified. The female to male ratio was 2:1. Five children had severe neonatal jaundice. Early milestones were normal in the majority. Neurologic symptoms generally developed between 5 and 10 years of age with a mean age of 7.2 years at diagnosis. Seizures developed in all between 4.5 and 16 years of age (mean, 10.5 yr), and were followed by significant physical and mental deterioration. The age at death ranged between 11 and 22.5 years (mean, 14.8 yr). In 61%, bronchopneumonia was the cause of death. There is significant variability in the presentation and clinical course of Niemann-Pick type D. (J Child Neurol 1998;13:75-78).

Although it is known that many stimuli can activate mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinases (PI3K) in human neutrophils, little is known concerning either the mechanisms or function of this activation. We have utilized a selective inhibitor of MAPK kinase (MEK), PD098059, and two inhibitors of PI3K, wortmannin and LY294002, to investigate the roles of these kinases in the regulation of neutrophil effector functions. Granulocyte/macrophage colony-stimulating factor, platelet-activating factor (PAF) and N-formylmethionyl-leucyl-phenylalanine are capable of activating both p44ERK1 and p42ERK2 MAPKs and phosphotyrosine-associated PI3K in human neutrophils. The activation of extracellular signal-related protein kinases (ERKs) is correlated with the activation of p21ras by both tyrosine kinase and G-protein-coupled receptors as measured by a novel assay for GTP loading. Wortmannin and LY294002 inhibit, to various degrees, superoxide generation, neutrophil migration and PAF release. Incubation with PD098059, however, inhibits only the PAF release stimulated by serum-treated zymosan. This demonstrates that, while neither MEK nor ERK kinases are involved in the activation of respiratory burst or neutrophil migration, inhibition of PAF release suggests a potential role in the activation of cytosolic phospholipase A2. PI3K isoforms, however, seem to have a much wider role in regulating neutrophil functioning.

In order to introduce more structure to the debate it seems worthwhile to make a rough cost-benefit analysis of the probable effects of the Dutch drug policy in various areas. A multi-disciplinary analysis of this nature makes it possible to bring together the arguments put forward by the protagonists from various perspectives and to some extent balance them against each other. In a traditional cost-benefit analysis the anticipated effects are assessed in financial terms. This is only possible to a very limited extent when it comes to drug policy. The article is limited to cataloguing as fully as possible the most significant pros and cons of the Dutch drug policy found in the literature on the subject. As a conclusion attention is paid to whether changes such as ‘decriminalisation’ or ‘re-criminalisation’ of drug use will yield a better cost-benefit analysis against the background of this overview.

The antitumour activity of S 16020-2, a new topoisomerase II inhibitor, was evaluated in comparison with doxorubicin against 13 human tumours, including colon (HT-29, Colo320DM), breast (MCF7, MDAMB-231), ovary (SK-OV-3, A2780, NIH:OVCAR-3), non-small cell lung (NCI-H460, A549, Calu-6, NCI-H125) and small-cell lung (NCI-H69, SCLC6) cancers. S 16020-2 was administered weekly intravenous within a dose range of 20-90 mg/kg for 3 weeks. Antitumour responses were obtained in all the tumour types tested except in the two colon cancers. S 16020-2 produced significant growth delays in nine tumour models and induced regressions of all A549 lung tumours. The antitumour activity of S 16020-2 was superior to that of doxorubicin against the NCI-H460, A549, NCI-H69, SCLC6 and NIH:OVCAR-3 xenografts. These results demonstrate the broad spectrum of antitumour activity of S 16020-2 in a large panel of in vivo experimental models and confirm its interest as a potential agent in the treatment of malignant disease.