Demographic and clinical features of glutaric acidemia type 1; a high frequency among isolates in Upper Egypt

Glutaric acidemia type 1 [GA1] was thought to be a rare disorder in Arab countries. Recently, a relatively large number of patients with GA1 have been detected in Egypt. The aim of this work was to: [1] find out the commonest clinical characteristics of the disease among Egyptians presenting with GA1; [2] delineate the demographic factors that may lead to a high prevalence of GA1 among Egyptians; [3] Recommend the most suitable strategy to screen for the disease. The study included all patients with GA1 who presented at The Genetics Unit, Ain Shams University Hospital [GUASH] during the last three years. The information about patients with GA1 including the epidemiological and clinical data was obtained retrospectively from patients' files. The authors surveyed data of 26 patients in 23 families who were personally examined and the diagnosis was confirmed by laboratory data. The mean age of onset of symptoms was 5.8 +/- 2.2 months: the mean delay in establishing the diagnosis was 11.73 +/- 13.97 months. At the onset of symptoms, macrocephaly [85%] was the commonest feature of GAI followed by dystonia [69%], and persistent convulsions [50%]. Onset of symptoms occurred during an acute febrile illness in 68% of patients, which was associated with the worst forms of dystonia [X2 = 12.5, p =0.14]. The frequency of affected Christian families among all affected families was 43%, which is significantly higher than that expected of the Christian minority in Egypt [6-15%]. There has been no significant increase in consanguinity among those Christian families [F = 0.014204] pointing to a high gene frequency of GA1 in isolated areas in Upper Egypt. In the absence of mass newborn screening program, continuous Health Education program should be implemented to promote detection of early signs of GA1 such as macro-cephaly before the occurrence of acute crisis of encephalopathy especially in families with history of similar patients. We recommend that a nationwide program of extended tandem mass screening should cover all newborns in Egypt to promote early detection of patients with GA1 and to avoid the severe consequences of the delay in diagnosis

Screening of diseases associated with abnormal metabolites for evaluation of HPLC in organic aciduria profiling

Organic acid disorders are a heterogeneous group of inborn errors of metabolism, in which organic acids accumulate in the body. They have high prevalence in Egypt because of a high rate of consanguineous marriages. Here we report our experience with the diagnostic evaluation of patients with organic acidemias as well as several other inborn errors of metabolism [lEMs] by liquid chromatography-tandem mass spectrometry [LC/MS-MS], gas-chro-matography mass spectrometry [GC/MS] and by isocratic cation exchange [high-performance liquid-chromatography] [HPLC] to evaluate the use of HPLC method for disease-associated metabolite screening. In this study, we screened 86 suspected Egyptians patients with organic acid disorders by LC/MS-MS, GC/MS and by HPLC aged from 3 days to 12 years old. Data obtained from the three methods were statistically analyzed to evaluate the specificity and sensitivity of the HPLC method over the other two methods and to pursue its precision in the diagnosis of organic acid disorders. Moreover, 17 urine samples were collected from patients with several other lEMs to evaluate the efficiency of HPLC in detecting abnormal metabolites in urine samples. The screening results showed that diagnostic efficiencies were varied among the three methods, HPLC showing a higher sensitivity of detecting normal urine as well as a highly satisfactory extent for the detection of different metabolic disorders. In addition, some typical urinary HPLC chromatograms of different metabolic disorders were presented to help the investigator who is going to start an organic aciduria screening program by HPLC to be familiar with various patterns. This study has indicated that HPLC is an easy applicable and useful technique for the initial screening of organic acid disorders and many other disease associated metabolites

Relation between smoking and cognition in egyptian elderly

In spite of numerous studies published in the past few years on the topic, the effectof smoking on Alzheimer's disease and dementia remains uncertain. Case-control studies havelargely suggested that smoking lowers the risk of AD, whereas prospective studies have shownthat smoking increases this risk or has no effect on the probability of developing AD. The aim of this study is to compare the prevalence of Smoking in elderly withcognitive impairment and elderly with non-cognitive impairment. A Case control 88 participants aged 60 years and above. They wereselected from Ain Shams University Hospital from inpatient wards and outpatient clinics. Thestudied sample was divided into 3 groups: Group A [32 elderly patients with Alzheimer's disease],Group B [32 elderly patients with Mild cognitive impairment] and Group C [24 controls withnormal cognitive function].Comprehensive geriatric assessment, including detailed history, physicalexamination, and also cognitive assessment using Montreal Cognitive Assessment [MOCA] andMini mental status examination [MMSE].As regards smoking there was a highly statistical significant difference between the 3groups as non-smokers were more prevalent in Alzheimer's diseaseand Mild cognitiveimpairment groups in comparison to control group with [p-value= 0.001]. There was a highly significant negative association between smoking and cognitiveimpairment

Role of intestinal microflora [Lactobadllus Acidophilus] in phagocytic function of leukocytes in type 2 diabetic patients

The prevalence of obesity, insulin resistance and type 2 diabetes has steadily increased in the last decades. In addition to the genetic and environmental factors, gut microbiota may play an important role in the modulation of intermediary phenotypes leading to metabolic disease. Infection is an important cause of morbidity and mortality in diabetic patients. Chronic hyperglycemia impairs host defense mechanism such as cell mediated immunity, polymorphonuclear leukocyte function, and antibody formation. So we aimed to study the association between intestinal microflora [Lactobacilles acidophilus] count and phagocytic activity of polymorphonuclear leukocytes in humans with type 2 diabetes. The study included 20 type 2 diabetic patients with good glycemic control and 20 type 2 diabetic patients with poor glycemic control. In addition, 20 normal healthy subjects were included as normal controls. The fecal composition of L. acidophilus was detected using de Man Rogosa Sharp agar followed by further confirmation using the polymerase chain reaction technique. Phagocytic function of polymorphonuclear leukocytes was assessed using the phagocytosis index%. Fecal L. acidophilus count was significantly increased among uncontrolled diabetic patients, while the phagocytosis index% was significantly reduced among the same patients. In uncontrolled diabetics, a significant positive correlation was observed between fecal L. acidophilus count and HbA1c and a significant negative correlation between phagocytic activity and L. acidophilus count. In conclusion, type 2 diabetes is associated with compositional changes in fecal L. acidophilus especially in the uncontrolled diabetes. The levels of glucose tolerance or severity of diabetes should be considered while linking the level of intestinal microbiota with a phagocytosis index of leukocytes

Genotoxicity of cadmium in rat lung cells assessed by an alkaline comet assay and the possible protective role of selenium

Cadmium is a highly toxic heavy metal with many hazardous effects. Selenium is an essential trace element with antioxidant properties. To evaluate the cadmium-induced DNA damage in rat lung cells and the possible protective role of selenium. Thirty-six adult male albino rats were used in this experiment. They were divided into four equal groups. Group I was the control group. Group II included rates that were injected intraperitoneally with cadmium chloride [CdCl[2]] [1.0 mg/kg/day] for 8 weeks. Group III included rates injected intraperitoneally with sodium selenite [Na[2]SeO[3]] [0.25 mg/kg/day] for 8 weeks. Group IV included rats injected intraperitoneally with both CdCl[2] [1.0 mg/kg/day] and Na[2]SeO[3] [0.25 mg/kg/day] for 8 weeks. At the end of the experiment, the lungs of rats were taken and processed for single-cell gel electrophoresis [comet assay]. In the control group, comets appeared with large bright heads and small tails. The injection of CdCl[2] in group II induced DNA damage in rat lung cells, indicated by increased migration in the comet assay. Comet cells appeared with small heads and long tails. Statistically, there was a significant increase in tail length, tail moment, and tail% DNA compared with the control. Injection of selenium alone did not show any difference from the control. Concomitant administration of both cadmium and selenium resulted in a partial decrease in the DNA damage in rat lung cells indicated by decrease in DNA migration in the comet assay. Comet cells appeared with large heads and relatively small tails compared with those of group II. A significant decrease was also observed in tail length, tail moment, and tail% DNA compared with group II. CdCl[2] could significantly induce DNA damage in rat lung cells. It was suggested that selenium could partially ameliorate DNA damage induced by cadmium

CXCR3 and CXCR4 receptors expression on peripheral blood T-lymphocytes from patients with rheumatoid arthritis

Rheumatoid arthritis [RA] is a chronic inflammatory condition that affects multiple joints. Chemokines and their receptors are involved together in the development and perpetuation of inflammation Chemokine receptors CXCR3 and CXCR4 are among the main regulators of T cell recruitment in autoimmune diseases. The present study aimed at detection of the frequency of CXCR3 and CXCR4 chemokine receptors expression on peripheral blood T-lymphocytes in patients with rheumatoid arthritis in an attempt to identify suitable targets for therapeutic intervention. Twenty eight patients with rheumatoid arthritis, selected from those attending the Rheumatology and Rehabilitation outpatient clinic, Ain Shams University Hospitals, were studied. Ten age and sex matched healthy subjects were served as controls. All patients were subjected to full medical history, thorough clinical examination, evaluation of the disease activity using disease activity score 28 [DAS28] and radiological assessment by plain X rays of both hands and feet [posterior - antero views] for the erosive changes. Peripheral blood lymphocytes analysis was performed by flow cytometry using anti-CD3, anti-CXCR3 and anti-CXCR4 monoclonal antibodies. High statistically significant difference was determined between patients and controls as regard relative count of T- lymphocytes expressing CXCR4 receptors [35.068 +/- 5.098, 23.59 +/- 4.601, respectively and P< 0.001]. Also, there was a significant positive correlation between relative count of T- lymphocytes expressing CXCR4 receptors and disease activity using disease activity sore 28 [DAS28] disease duration and the hemoglobin level. On the other hand, no significant correlation was determined between relative count of T- lymphocytes expressing CXCR3 receptors and any of the clinical and laboratory parameters of patients. Increased expression of CXCR4 on peripheral T cells of Patients [RA Patients] and its positive correlation with the disease activity indicate that this chemokine receptor plays a central role in the process of chronic inflammation in RA and suggests that targeting CXCR4 could provide a new treatment for this disease. Although our data did not prove that CXCR3 expression is higher in patients with RA, however, it can be expected that it is involved in the inflammatory process based on reported functional studies

Anti-hepatotoxic effect of pterocephalus sanctus growing in Egypt

Pterocephalus sanctus Decne. was subjected to a bioassay guided fractionation in order to follow and identify the active principles that could be responsible for its anti-hepatotoxic property. The aqueous methanol [80%] extract of the defatted powder of Pterocephalus sanctus was chromatographed over silica gel and eluted with gradient petroleum ether/ethyl acetate. Eight fractions were collected and tested for their biological activity using Primary Cultured Monolayer Hepatocytes where the fifth fraction was subjected to a further fractionation. Three compounds were identified as secologanin, loganin and swerosoid and the latter was only found to possess highly anti-hepatotoxic activity. This is the first report of the study of the anti-hepatotoxic activity of P. sanctus growing in Egypt

Study of interlukin-18 in viral hepatitis C patients with chronic hepatitis and hepatocellular carcinoma

Hepatitis C virus [HCV] infection represents a serious threat to human health; often resulting in liver cirrhosis and hepatocellular carcinoma [HCC]. The exact mechanisms responsible for persistent infection and long -term hepatocellular injury are poorly understood. It is hypothesized that the pro-inflammatory cytokine IL-18 may have an important role in chronic cellular immune response towards hepatocytes in the course of the disease. Of this study was to evaluate the significance of measuring IL-18 mRNA in peripheral blood mononuclear cells [PBMCs] in viral hepatitis C patients with chronic infection and HCC. Forty selected patients with chronic HCV infection [12 with compensated liver functions "group I" ; 12 with decompensated liver functions "group II"; and 16 with HCC on top of chronic HCV infection "group III"] and 10 healthy controls with matched ages and sex were studied. Using reverse- transcriptase polymerase chain reaction [RT-PCR], detection of HCVRNA in blood of patients and quantitation of IL-18 mRNA transcripts in PBMCs of patients and control were performed. This study showed a significant increase [p<0.001] in the mean value of transcriptional expression of IL-18 gene [as a ratio to that of beta-globin] in PBMCs in all patients groups compared to control. A positive [however insignificant] correlation was detected between transcriptional expression of IL-18 gene and serum albumin [r=0.446]; ALT[r=0.074] as well as prothrombin time [r=0.332] in chronic viral hepatitis patient groups [compensated and decompensated]. A significant positive correlation was found between transcriptional expression of IL-18 gene and hepatitis C viral load in all patient groups[r=0.756; 0.669; and 0.956 respectively]. These results support the hypothesis that IL-18 has an important role in the immunopathogenetic events leading to liver injury in chronic HCV infection. The antiviral action of IL-18 might be counteracted by multiple factors leading to persistent HCV infection [as IL-10]. The question becomes important whether and to what extent the HCC is influenced by IL-18. Future follow- up studies are recommended to investigate the role of monoclonal antibody to IL-18 in amelioration of liver damage and cirrhosis in such patients, in addition to further studies to highlight the role of IL-18 binding protein [BP] and Th-2 cytokines [as IL-10] as possible antagonists to the antiviral action of IL-18. Finally future- large scales studies correlating IL-18 gene expression with markers of HCC progression are recommended to gain insight into the antitumor action of IL-18 as it would be a promising new strategy to control HCC

Histological study of the effect of potassium bromate on the thyroid gland of adult male albino rats and the protective role of vitamin C supplementation

Thirty adult male albino rats were used in this study aiming to study the effect of chronic oral administration of potassium bromate on the structure of the thyroid gland and to study the possible protective role of the concomitant supplementation of vitamin C. The animals were divided equally into three groups [10 animals each]; a control group and two experimental ones. The animals of the first experimental group were subdivided equally into 2 halves. The animals of the first half were given a daily oral dose of potassium bromate 30 mg/kg body weight for successive 2 months. While the animals of the other half were given the same daily oral dose of potassium bromate for successive 6 months. The animals of the second experimental group were also subdivided equally into 2 halves. These animals were given a daily intraperitoneal injection of 20 mg/kg body weight of vitamin C for 2 and 6 months respectively simultaneous with a daily oral dose of potassium bromate as in the first experimental group. At the time of sacrifice, all the animals of each group were anaesthetized with ether inhalation and their thyroid glands were dissected out carefully and processed for light and electron microscope examinations. Light microscope observations of the thyroid glands of the potassium bromate treated rats for 2 months revealed alterations of many thyroid follicles. Their follicular cells became squamous with deeply stained nuclei. Ultrastructurally, the follicular cells contained irregular heterochromatic nuclei. Their cytoplasm contained dilated rough endoplasmic reticulum and swollen mitochondria. Mast cells were seen in the connective tissue between the affected follicles. Light microscope examination of the thyroid glands of the rats treated with potassium bromate for 6 months showed loss of the architectures of the glands. The follicular cells appeared with deeply stained nuclei and marked cytoplasmic vacuolations. Ultrastructrually, the follicular cells contained dilated and fragmented rough endoplasmic reticulum. Their nuclei showed irregular outlines and much clumps of heterochromatin. While light and electron microscope examinations of the thyroid glands of the animals treated with vitamin C concomitant with potassium bromate revealed preservation of the architectures of the glands. Most of their follicles appeared with few colloid. The follicular cells contained well developed rough endoplasmic reticulum with some dilated cisternae, numerous mitochondria with few swollen ones and cytoplasmic vacuolations. In conclusion, the results of this study revealed that chronic oral administration of potassium bromate led to structural changes in the thyroid gland which were duration dependant. Vitamin C supplementation with potassium bromate showed a moderate protection against these alterations

Laparoscopic vertical banded gastroplasty versus laparoscopic adjustable gastric banding in morbidlty obese patients: a comparative study

To compare between laparoscopic vertical banded gastroplasty and laparoscopic adjustable gastric banding as regard the operative procedure, efficiency, clinical results and complications, in the treatment of morbid obesity A total of 40 morbidly obese patients, with body mass index [BMl] 40 to 50 kg/m[2] were selected to either laparoscopic adjustable silicone banding [LASGB] [n = 21 cases] or laparoscopic vertical banding gastroplasty [LVBG] [n 19 cases]. The patients were operated upon during the period between February 2000 to November 2001 with a follow up period of 24 months postoperatively There were no deaths in both groups but conversions to open surgery in one case in [LVBG]. Mean operative time was 94.2 minutes in [LVBG] versus 65.4 minutes in [LASGB] [P < 0.05] Early morbidity rate was lower in LASGB [6.1%] versus LVBG [9.8%]. Mean hospital stay was shorter in LASGB [3 days] versus LVBG [6 days [P < 0.05,]. Late complications in LVBG was 14% and in LASGB was 32.7% [P < 0.05]. The most frequent complication was slippage of the band [18%]. Late reoperations rate in LVBG was 0% versus 24.5% in LASGB [P < 0.001]. Weight loss in LVBG after 2 years was [63.5%], versus 41.4% in LASGB. BMI in L VBG at 2 years was 29.7 kg/m[2] versus 34.8kg/m[2] in LASGB. This study demonstrates that, in patients with BMI 40 to 50 kg/m[2], LASGB requires shorter operative time and hospital stay but LVGB is more effective in terms of late complications reoperations and weight loss

Low birth weight: incidence and obstetric risk Factors in Riyadh, Saudi Arabia

Low birth weight [LBW] is a major determinant of perinatal survival and postnatal morbidity. It is an indicator of socioeconomic development of the community. In this study we determined the occurrence of LBW among Saudi newborns and its relation to the obstetric history of their mothers. The birth weight of all Saudi infants born in King Khalid University Hospital [KKUH] between 1992 and 1995 and the obstetric history of their mothers were investigated. A total of 14747 newborn were included in the study, their weight ranged from 500-7000 g. The incidence of LBW [<2500 g] was 7.7%. [1141]. Results of multivariate logistic regression showed that the major obstetric risk factors are maternal age < 20 years [OR = 1.41, CI.07-1.85], primiparity [OR=1.41, CI.11-1.77], prematurity [OR=53.72, CI=45.66-63.21] and female newborn [OR=1.36, CI=1.17 -1.58]. Multiparity [>/= 5 deliveries] and history of abortion were not found to have significant statistical association with LBW. This study shows that simple parameters that are commonly collected by health workers can be helpful in prediction of the possibility of having a LBW newborn

Interstitial deletion of the long arm of chromosome 3

Interstitial deletion of chromosome 3 with breakpoints at bands 3q23 - 3q25 has been reported in a few cases. We report here a patient with del [3] [q23q25.3], who presented with dysmorphic features common to other reported cases. However, the dysmorphism was less marked suggesting that the clinical features are variable in this syndrome

Concentrations of-plasma atrial natriuretic peptide, renin, angiotensin II and aldosterone under different conditions of sodium intake in rats

It is known that atrial natriuretic peptide [ANP] plays a major role in the homeostasis of body fluids. There are evidence that ANP may link the heart, kidney, adrenal, blood vessels and brain in a complex system involved in the regulation of body fluids and electrolytes as well as blood pressure. The study was carried out on 90 male albino rats divided into 6 groups, each of 15 rats. The first group was kept for 15 days on normal diet [controls], the 2nd, 3rd groups were kept on different sodium intake, 50, 150 and 350 nmol/kg of diet respectively. The 5th group was injected daily with 0.01 micro l/kg body weight ANP and the last group was injected daily with 0.02 micro l/kg body weight cafedrine HC1, theodrenaline HC1 for 7 days. At the end of the experiments the animals were sacrificed, blood samples were obtained and plasma separated and kept frozen for analysis. The results show that plasma ANP, renin, aldosterone and angiotensin II were significantly decreased in the 3rd, and 4th groups while in the 2nd group there was no statistically significant change when compared with controls. After injection of cafedrine, HC1, theodrenaline HC1, plasma ANP was significantly decreased while plasma renin, aldosterone and angiotensin II were significantly increased. After injection of ANP, significant decrease in renin and aldosterone was observed but angiotensin II showed significant decrease. Plasma sodium and potassium concentrations were significantly increased in all cases compared to controls. The results were discussed according to current literatures

Beta adrenergic blockade in asthmatic children and the effect of bronchodilators

The beta adrenergic function was assessed in 30 asthmatic and 15 healthy children by measuring the epinephrine induced rise in urinary cAMP excretion. Asthmatic children excreted less cAMP, especially when suffering from respiratory distress. In addition, they showed subnormal rise in urinary cAMP excretion following s.c. epinephrine injection. Oral aminophylline and prednisone increased both basal and epinephrine-induced response in cAMP excretion by asthmatic children. No such effects were observed after oral ephedrine. Beta adrenergic blockade appears to be a basic abnormality in the pathogenesis of bronchial asthma. Bronchodilator drugs are not responsible for this blockade. On the contrary, aminophylline and prednisone appear to help overcome this blockade

Androgen-estrogen imbalance in schistosomal hepatic fibrosis

Twenty male patients with schistosomal hepatic fibrosis with feminization characters were studied and compared with 10 adult healthy controls. The total urinary excretion of 17 ketosteroids and its fractionation, dehydroisoandrosterone, Androsterone and etiocholanolone were significantly lower than control, whereas the urinary excertion of total estrogens, including estrone, estradiol, 17B and Estriol were significantly higher than control, reflecting increased circulating blood estrogens. There was a good correlation between these hormonal changes and feminization characters, but not with impairment of liver function, indicating that sex hormones metabolism by the liver is a highly specific and specialized function that may be completely unrelated to the other liver functions. The development of gynaecomastia in our series [75%] may be due to a combination of stimulation of prolactin secretion by the high blood estrogen, the latter may exert a direct stimulatory effect on the mammary gland, alternatively decreased androgen production removes the antagonistic effect of androgen on estrogen in the breast

Androgen estrogen imbalance in bilharzial hepatic fibrosis

20 adult male patients with bilharzial hepatic fibrosis and feminzation features [8 ascitic and 12 non-ascitic] as well as 10 controls were studied clinically and biochemically for the determination of total 17-ketosteroids, dehydroisooadrosterone, androsterone and etiocholanolone. total estrogens, estradiol-17 B, estrone and estriol It was found that puberty never occurred in 11 patients with loss of libido and impotence. Infantlism was found in 4 of these 11 cases. The remaining 9 patients in whom puberty occurred, decreased libido was recorded in 4 cases and impotence present in the other 5 caes. Testicular atrophy was present in 16 of the 20 cases. Decreased body hairs with feminine distribution was present in 16 cases. Gynaecomastia was present in 15 patients Data obtained showed that the daily excretion of total estrogens, estrone, estradiol 17B and estradiol were much higher in the cases studied as compared to normal controls. The differences were statistically significant. The mid 24 hour urinary excretion values of total 17-ketosteroids dehyroisanrosterone, androsterone and etiocholanolone were significantly much lower in the cases when compared with controls