A randomized placebo-controlled, double-blind study to investigate the effect of a high oral loading dose of cholecalciferol in non-alcoholic fatty liver disease patients, new insights on serum STAT-3 and hepassocin.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver metabolic disease affecting millions globally. This study aimed to assess the safety and efficacy of a high oral loading dose of cholecalciferol supplement on NAFLD patients and to investigate its potential role on serum inflammatory biomarkers. PATIENTS AND METHODS: One hundred patients with NAFLD and type 2 diabetes mellitus were involved in the study. Eligible patients were randomized among two equal groups. Group 1 received the standard conventional therapy in addition to a placebo. Group 2 received the conventional therapy plus cholecalciferol for 4 months. The improvement in the patients' glycaemic control parameters, liver function tests, lipid profile, and serum 25-hydroxy vitamin D at the end of the study was set as a primary outcome. The secondary outcome was the decrease in steatosis grade in the ultrasound and high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), signal transducer and activator of factor-3 (STAT-3), nitric oxide (NO), malondialdehyde (MDA), and hepassocin serum levels at the end of the study. RESULTS: Group 2 revealed a significant reduction in the serum levels of lipid profile measures, hs-CRP, alanine aminotransferase (ALT), STAT-3, NO, hepassocin, and MDA compared to the baseline and group 1 results. Whereas group 1 did not show these significant changes. Both groups observed no significant changes in glycemic index, TNF-α, aspartate aminotransferase (AST), and albumin levels. CONCLUSIONS: Cholecalciferol is recommended as additional therapy to modulate lipid peroxidation and systemic inflammation alongside other NAFLD therapies.

Time to go wireless? A 15-year single institution experience of radioisotope occult lesion localisation (ROLL) for impalpable breast lesions.

INTRODUCTION: Wire guided localisation (WGL) is the standard localisation technique for impalpable breast lesions. Radio-guided occult lesion localisation (ROLL) has been proposed as an alternative. We have been performing ROLL for therapeutic wide local excisions (WLE) and diagnostic excision biopsies (DEB) for the last 15 years. We present the largest reported consecutive series of ROLL excisions to date. PATIENTS AND METHODS: One thousand thirty nine consecutive patients who underwent ROLL for impalpable breast lesions were identified from a prospectively collected database. 673 patients underwent WLE and 366 patients underwent DEB. Data were analysed from proformas completed at the time of the procedure by the radiologist and operating surgeon. These data were supplemented with an analysis of patient electronic records including specimen radiograph and histopathology reports. RESULTS: 99.1% of ROLL WLE revealed histological diagnoses of invasive cancer or DCIS. 98.7% of radiological abnormalities were identified on WLE post-excision radiographs (97.5% following DEB). Complete excision was recorded in 79.0% of the WLE patients following histological evaluation. 31.7% of DEB cases were pathologically upgraded to a malignant diagnosis. The presence of microcalcification, preoperative underestimation of the lesion size and symptomatic referral predisposed to incomplete excision status. DISCUSSION: ROLL is a safe and effective technique to localise impalpable breast lesions. In addition ROLL has potential technical and logistic advantages over WGL.

AMH gene mutations in two Egyptian families with persistent müllerian duct syndrome.

The anti-müllerian hormone (AMH) is responsible for regression of müllerian ducts during male sexual differentiation. Mutations in the AMH gene or its type II receptor gene AMHR2 lead to persistence of the uterus and fallopian tubes in male children, i.e. persistent müllerian duct syndrome (PMDS). Both conditions are transmitted according to an autosomal recessive pattern and are symptomatic only in males. We report on 2 unrelated Egyptian consanguineous families with PMDS. The first family comprised 3 affected prepubertal sibs complaining of undescended testes. Pelvic exploration and laparotomy revealed müllerian duct derivatives. The other family was presenting with an adolescent male with impalpable left testis, and pelvic exploration showed remnants of fallopian tubes and rudimentary uterus. AMH levels were very low and almost undetectable in all affected patients in both families. Direct sequencing of the coding region of the AMH gene identified 2 homozygous mutations in exon 1, R95X in the first family and V12G in the second family. These data confirmed the autosomal recessive type of PMDS. Molecular investigation of this rare disorder in a larger number of cases with undescended testes in Egypt is warranted for proper diagnosis and genetic counseling.

Homozygosity for a novel missense mutation in the leptin receptor gene (P316T) in two Egyptian cousins with severe early onset obesity.

Congenital deficiency of the leptin receptor is a very rare cause of severe early-onset obesity. To date, only 9 families have been reported in the literature to have mutations in the leptin receptor gene. The clinical features include severe early onset obesity, severe hyperphagia, hypogonadotropic hypogonadism, and T cell and neuroendocrine/metabolic dysfunction. Here we report two cousins with severe early onset obesity and recurrent respiratory tract infections. Their serum leptin levels were elevated but they were within the range predicted by the elevated fat mass in both cousins. Direct sequencing of the entire coding sequence of the leptin receptor gene revealed a novel homozygous missense mutation in exon 6, P316T. The mutation was found in the homozygous form in both cousins and in the heterozygote state in their parents. This mutation was not found in 200 chromosomes from 100 unrelated normal weight control subjects of Egyptian origin using PCR-RFLP analysis. In conclusion, finding this new mutation in the LEPR beside our previous mutation in the LEP gene implies that monogenic obesity syndromes may be common in the Egyptian population owing to the high rates of consanguineous marriages. Further screening of more families for mutations in LEP, LEPR, and MC4 might confirm this assumption.

The most encountered groups of genetic disorders in Giza Governorate, Egypt.

This study presents the prevalence, relative frequency, and analysis of genetic diseases/malformations in 73260 individuals. Cases included were ascertained from: Pediatric outpatient clinics of two governmental hospitals and two primary health care centers (PHCCs) in Giza Governorate; Neonatal intensive care unit (NICU) in the selected hospitals and Outpatients Human Genetics Clinics (NRC). 62819 persons visited the outpatients clinics of selected hospitals and PHCCs in Giza governorate. Out of these persons 731 cases (1.16%) proved to have known genetic disorders or malformations. 7755 neonates were delivered in the selected hospitals. Out of these neonates 666 newborns entered NICU and 3% (20 neonates) of them had genetic or congenital disorders. Also, 2686 patients were ascertained from the Human Genetics Clinics, NRC. The overall parental consanguinity rate among the 3417 diagnosed cases was 55%, ranging from 29.5-75%. The study showed a high prevalence of genetic/malformation disorders among Egyptians, with frequencies comparable to other Arab populations (Tab. 4, Ref. 25). Full Text (Free, PDF) www.bmj.sk.

Screening of genital anomalies in newborns and infants in two egyptian governorates.

BACKGROUND: External genital anomalies are among the most common congenital anomalies. Proper early diagnosis and management of genital abnormalities are of great importance to minimize medical, psychological and social complications. AIM: To detect the incidence of external genital anomalies and disorders of sex development (DSD) in Great Cairo and Qalyubiyah governorates. SUBJECTS AND METHODS: 20,000 newborns and infants up to the age of 6 months coming for compulsory vaccination at primary health care units and centers in Great Cairo and Qalyubiyah governorates were examined in the years 2006-2007 for suspected genital anomalies. RESULTS: There were 187 (93.5/10,000) cases with external genital anomalies among the screened 20,000 participants. Various abnormalities in the form of 46,XY DSD, undescended testis, hydrocele, hypospadias, micropenis, synechia of the labia and other genital anomalies were diagnosed and classified after thorough clinical examination, and hormonal, radiological, and laparoscopic investigations. CONCLUSION: This first pilot study in Great Cairo and Qalyubiyah governorates showed a relatively high incidence of genital anomalies and DSD. Therefore, we recommend more studies including larger population sizes to detect the actual incidence of genital anomalies and DSD in Egypt in order to serve those patients and their families.

A novel homozygous missense mutation of the leptin gene (N103K) in an obese Egyptian patient.

Congenital leptin deficiency is a rare recessive genetic disorder resulting in severe hyperphagia and early onset obesity. It is caused by mutations in the LEP gene encoding leptin. To date, only two mutations have been identified in the LEP gene, Delta133G and R105W. We present the third reported mutation identified in an Egyptian patient with very low serum leptin levels and severe early onset obesity (BMI = 51). Direct sequencing of the coding region of the LEP gene revealed a novel homozygous missense mutation, N103K. The N103K mutation was not found in 100 alleles from 50 unrelated Egyptian normal-weight control subjects using polymerase chain reaction and restriction fragment length polymorphism analysis. In conclusion, this study presents the third reported mutation of the LEP gene and will provide further insight into the physiologic role of leptin in human obesity.

Differential diagnosis of disorders of sex development in Egypt.

BACKGROUND: Disorders of sex development (DSD) with birth of an infant with ambiguous genitalia require medical attention to elucidate the differential diagnosis. This group of disorders is not uncommon in Egypt (1:3,000 livebirths). AIMS: We want to provide an extensive review of a patient collective with ambiguous genitalia from 6 years experience at the Department of Clinical Genetics at the National Research Center in Egypt. METHODS: 208 patients with ambiguous genitalia were recruited from the genetic clinic from 2000 to 2005. They were subjected to history taking, pedigree analysis. Full clinical examination, cytogenetic study, hormonal, radiological investigations, and molecular studies were performed where possible. RESULTS: 46,XY DSD was more common than 46,XX DSD constituting 65.9% of total cases. Consanguinity was high with 61% in the affected families; however, only 21 cases had a positive family history. There was preference of male sex of rearing (regardless of karyotype), despite a severe degree of ambiguity. CONCLUSION: Disorders of sex development have a broad range of underlying causes also in Egypt with some preference of rare monogenic disorders. For improving diagnostic standards, the provision of centers of tertiary pediatric care is recommended for patients with DSD even in developing countries.

Phenotypic and cytogenetic spectrum of 9p trisomy.

Trisomy 9p is one of the most frequent autosomal anomalies compatible with long survival rate. The spectrum of clinical severity in trisomy 9 roughly correlates with the extent of trisomic chromosome material. Trisomy 9p is a clinically well delineated syndrome and of all stigmata craniofacial dysmorphism is most specific. In this study we report five cases with de novo trisomy 9p. The study aimed at the identification of the genotype/phenotype correlations in patients with different breakpoints. GTG banding, DAPI stain, whole chromosome paint, centromere, telomere and 9p21 specific locus probes demonstrated that partial trisomy 9p in case 1 was due to isochromosome 9p with translocation of the long arm of re-arranged chromosome 9 onto the short arm of chromosome 13, cases 2 and 3 had intrachromosomal duplication of the short arm of chromosome 9 [dup(9)(p21p24)], case 4 had "classical" 9p trisomy and case 5 had duplication of whole short arm and part of the long arm of chromosome 9 (partial 9 trisomy). Although cases 1 to 4 had trisomy involving 9p, cases 1 and 2 exhibited the classical clinical manifestations of 9p trisomy, while cases 3 and 4 had additional features overlapping with Coffin-Siris syndrome. The present study strengthens the association of Coffin-Siris syndrome and 9p, the significance of such observations may point to possible gene location of Coffin-Siris syndrome on 9p. Case 5 had additional manifestations more than those typical of trisomy 9p which could be due to duplication of 9q21 region. Wide gap between 1st and 2nd toes, observed in the studied cases, can be added to the phenotype of this trisomy. Three of our cases had brain malformations, case 3 had dilated ventricles with hypogenesis of corpus callosum, case 4 had agenesis of corpus callosum, and case 5 had Dandy-Walker malformation. We also suggest that dosage effects of genes located in 9pter-q22 contribute to the etiology of Dandy-Walker syndrome. We recommend MRI studies as a routine in all cases with trisomy 9p.

Unusual pattern of inheritance and orodental changes in the Ellis-van Creveld syndrome.

Ellis-van Creveld (EVC) syndrome (chondroectodermal dysplasia, mesoectodermal dysplasia, OMIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth. Oral manifestations tend to be pathognomonic such as multiple broad labial frenula and congenital missing teeth. In this study we report three Egyptian families with six cases of EVC syndrome. An unusual pattern of inheritance with father to son or to daughter transmission was observed in 2 consanguineous families thus demonstrating pseudo-dominant inheritance, probably for the first time in the literature. A new consistent orodental anomaly found in all our cases was bifid tip of the tongue. We emphasize study of orodental anomalies in future cases for accurate diagnosis of Ellis-van Creveld syndrome and its probable differential diagnosis from Weyers acrodental dysostosis.

Modified technique for dilatation of difficult nephrostomy tracts.

Dilatation of a percutaneous nephrostomy tract often is a difficult step, especially in patients who had previous renal surgery. Initial use of the central rod of a telescoping metal dilator set with the backloaded first dilator allows us to avoid using the fascial dilators, which are not rigid enough to dilate the tough perirenal fibrous tissue. It also permits one-stage placement of the "safety" guidewire. This technique has proved so advantageous and convenient that we now use it routinely in all cases whether they are recent or recurrent.

Prophylactic antiemetic therapy with ondansetron, tropisetron, granisetron and metoclopramide in patients undergoing laparoscopic cholecystectomy: a randomized, double-blind comparison with placebo.

PURPOSE: Postoperative nausea and vomiting (PONV) is a distressing adverse effect of general anaesthesia. The aim of the current study was to compare the antiemetic activity of different 5-hydroxytryptamine3 receptor antagonists with that of metoclopramide and placebo. METHODS: In a prospective, randomized, double-blind study we have compared the antiemetic activity of the prophylactic administration of ondansetron 4 mg, tropisetron 5 mg and granisetron 3 mg with that of metoclopramide 10 mg and placebo in 132 patients undergoing laparoscopic cholecystectomy. All study drugs and placebo were given as a short iv infusion ten minutes before the induction of anaesthesia. Perioperative anaesthetic care was standardized in all patients. Nausea and vomiting were assessed by direct questioning of the patient at 1, 4, 9, 12, 18 and 24 hr after recovery from anaesthesia. If patients experienced nausea and/or vomiting, rescue antiemetic treatment (metoclopramide 10 mg iv) was administered. RESULTS: For the 24-hr recovery period after surgery, the percentages of emesis-free patients were 65.5%, 52%, 48%, 29.2% and 27.6% in the ondansetron, granisetron, tropisetron, metoclopramide and placebo groups, respectively. Prophylactic antiemetic treatment with ondansetron resulted in a lower incidence (P = 0.02) of PONV than with metoclopramide or placebo. The times at which rescue antiemetic was first received were longer (P < 0.01) in ondansetron group than in the placebo and metoclopramide groups. There were no statistical differences between ondansetron, tropisetron and granisetron groups. CONCLUSIONS: Ondansetron, when given prophylactically resulted in a significantly lower incidence of PONV than metoclopramide and placebo. Metoclopramide was ineffective.

Enzymatic antagonism of mivacurium-induced neuromuscular blockade by human plasma cholinesterase.

BACKGROUND: Mivacurium chloride is a bis-benzylisoquinolinium nondepolarizing neuromuscular blocking agent, hydrolyzed by butyrylcholinesterase (PCHE). The dose-response relationships for PCHE after mivacurium have not been studied. Therefore, this study was designed to establish dose-response relationships for PCHE as an antagonist of mivacurium-induced neuromuscular blockade. METHODS: Forty-eight physical status 1 adults were given 0.15 mg/kg mivacurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. Train-of-four (TOF) stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height (T1) reached 10% of its initial control value, exogenous PCHE equivalent to activity present in 2.5, 5, 7.5, 15, or 25 ml/kg of human plasma was administered by random allocation to 40 patients. Neuromuscular function in another eight subjects was allowed to recover spontaneously. Two blood samples were taken for determination of plasma cholinesterase activity. The first sample was taken before induction of anesthesia, and the second sample was taken when the TOF ratio had recovered to 0.75. Dibucaine and fluoride numbers were determined from the first assay. RESULTS: Administration of PCHE produced significant increases in PCHE activity in all patients. The larger the dose, the greater was the resultant plasma activity. Human PCHE produced a dose-dependent antagonism of mivacurium-induced neuromuscular blockade and the recovery times correlated inversely with PCHE activity (P < 0.01). The recovery of T1 was greater (P < 0.01) and time to attain a TOF ratio of 0.75 was shorter (P < 0.01) with any dose of PCHE than that observed in the spontaneous recovery group. After the administration of exogenous PCHE equivalent to activity present in 25 ml/kg of human plasma, recovery of TOF ratio to 0.75 or more was observed in all patients in less than 10 min and time to attain a TOF ratio of 0.75 was 55% shorter than the spontaneous recovery group (8.4 [7.1-9.7] vs. 18.7 [15.4-22] min; mean and 95% confidence intervals). CONCLUSIONS: Administration of exogenous PCHE equivalent to activity present in 25 ml/kg of human plasma (in a 65-kg patient, this dose is equivalent to PCHE activity of 1,625 ml of adult human plasma) resulted in reliable antagonism of mivacurium-induced neuromuscular blockade. Nevertheless, because of the prohibitive cost of this compound, this reversal modality is unlikely to have a routine practical application at this time.

Midazolam for caudal analgesia in children: comparison with caudal bupivacaine.

In a randomized, double-blind study we have examined the analgesic efficacy of caudal administration of midazolam, bupivacaine, or a mixture of both drugs in 45 children, undergoing inguinal herniotomy. They were allocated randomly into three groups (n = 15 in each) to receive a caudal injection of either 0.25% bupivacaine 1 ml.kg-1 with or without midazolam 50 micrograms.kg-1 or midazolam 50 micrograms.kg-1 with normal saline 1 ml.kg-1. There were no differences in quality of pain relief, postoperative behaviour or analgesic requirements between the midazolam group and the other two groups. Times to first analgesic administration (paracetamol suppositories) were longer (P < 0.001) in the bupivacaine-midazolam group than in the other two groups. Further, the bupivacaine-midazolam group received fewer (P < 0.05) doses of paracetamol than the bupivacaine group. Side effects such as motor weakness, respiratory depression or prolonged sedation were not observed in patients who received caudal epidural midazolam only. We conclude that caudal midazolam in a dose of 50 micrograms.kg-1 provides equivalent analgesia to bupivacaine 0.25%, when administered postoperatively in a volume of 1 ml.kg-1 for children following unilateral inguinal herniotomy.

Management of ureteral stones by extracorporeal shock wave lithotripsy using Lithostar lithotriptor.

In 282 patients 290 ureteral stones were treated with extracorporeal shock wave lithotripsy using the Lithostar lithotriptor. Stones were in the upper ureter in 198 units (68.3%), middle ureter in 36 (12.4%) and lower ureter in 56 (19.3%). The average stone mass was 11.9 mm. and the mean number of shock waves was 4,913 for all levels with a mean kv. of 16.9. The average number of sessions was 1.5 for all sites. Auxiliary measures in the form of ureteral catheterization were done in 24 patients (8.5%) and internal stenting in 12 (4.25%), all of whom had upper or middle ureteral stones. Disintegration of the stones was achieved in 99% of the upper, 93.7% of the middle and 91.7% of the lower ureteral stones. However, clearance of fragments within 3 months from the last session was achieved in 94.8% of the upper, 87.5% of the middle and 91.7% of the lower ureteral stones for an overall stone-free rate of 93.3%.

Induction dose-responses studies with propofol and thiopentone.

The relative potencies of propofol and thiopentone were assessed using different indicators of induction of anaesthesia: abolition of the response to verbal commands and eyelash stimulation. Log-probit dose-response curves for these end-points were determined 30, 60 and 90 s after induction in 96 unpremedicated ASA group I patients. For propofol, ED50 values for abolition of the response to verbal commands and eyelash stimulation at different time intervals were in the ranges 1.16-1.42 and 1.23-1.72 mg kg-1, respectively; corresponding ED95 values were 2.18-2.67 and 2.42-3.27 mg kg-1, respectively. For thiopentone, the calculated ED50 values for verbal commands and eyelash stimulation at the same time intervals were 1.81-2.23 and 3.55-3.40 mg kg-1; corresponding ED95 values were 5.11-6.29 and 6.41-6.70 mg kg-1, respectively. The potency ratio of propofol to thiopentone observed in this study varied from 1:1.27 to 1:2.88. It is concluded that a dose-response curve reflecting one end-point of anaesthesia cannot be used to define another end-point of anaesthesia.

Ketamine for caudal analgesia in children: comparison with caudal bupivacaine.

Fifty children undergoing inguinal herniotomy were allocated randomly to three groups to receive a caudal injection of either 0.25% bupivacaine 1 ml kg-1 with or without ketamine 0.5 mg kg-1 or ketamine 0.5 mg kg-1 with normal saline 1 ml kg-1. There was no significant difference in quality of pain relief, postoperative behaviour or analgesic requirements between the ketamine group and the two other groups. The bupivacaine-ketamine mixture provided better analgesia than the bupivacaine solution alone. Side effects such as motor weakness or urinary retention were not observed in the ketamine group.

An outbreak of acute haemorrhagic conjunctivitis caused by enterovirus 70 in Jeddah during 1985.

Seventy-five cases of acute haemorrhagic conjunctivitis (A.H.C.) were subjected to full ophthalmic, bacteriological, virological, serological as well as cytological examinations. The majority of cases presented with bilateral conjunctivitis (70 out of 75). Although follicular reaction was the earliest sign, yet subconjunctival haemorrhages were the most constant findings in all the cases. Enterovirus 70 was isolated in 57 cases from conjunctival swabs and in 43 cases from serum samples. Complement flaxation test was positive for enterovirus 70 in 42 cases but negative for coxsackie and adenoviruses. No primary role has been found for bacteria in the pathogenesis of A.H.C. in this outbreak. Cytological examination of conjunctival scrappings showed the characteristics cytopathic effect (CPE) of enteroviruses.