Sanjad-Sakati syndrome/Kenny-Caffey syndrome type 1: a study of 21 cases in Kuwait.

We studied 21 patients with Sanjad-Sakati syndrome (SSS) from 16 families. Parental consanguinity was recorded in 2 families (12.5%). All patients had severe intrauterine growth retardation, short stature, small hands and feet, blue sclera, deep-set eyes, microcephaly, persistent hypocalcaemia and hypoparathyroidism. Medullary stenosis was detected in 2 patients. Cytogenetic and fluorescent in situ hybridization studies were normal. All affected persons had homozygous deletion of 12 bp (155-166del) in exon 3 of the TBCE gene. All of the parents were heterozygous carriers of this mutation. The high frequency of SSS and low frequency of consanguineous marriages in this study may reflect a high rate of heterozygous carriers.

Sanjad-Sakati syndrome/Kenny-Caffey syndrome type 1: a study of 21 cases in Kuwait

We studied 21 patients with Sanjad-Sakati syndrome [SSS] from 16 families. Parental consanguinity was recorded in 2 families [12.5%]. All patients had severe intrauterine growth retardation, short stature, small hands and feet, blue sclera, deep-set eyes, microcephaly, persistent hypocalcaemia and hypoparathyroidism. Medullary stenosis was detected in 2 patients. Cytogenetic and fluorescent in situ hybridization studies were normal. All affected persons had homozygous deletion of 12 bp [155-166del] in exon 3 of the TBCE gene. All of the parents were heterozygous carriers of this mutation. The high frequency of SSS and low frequency of consanguineous marriages in this study may reflect a high rate of heterozygous carriers

Primary male infertility in Kuwait: a cytogenetic and molecular study of 289 infertile Kuwaiti patients.

Infertility is one of the major public health problems, affecting 15% of couples who attempt pregnancy; in 50% of these, the male partner is responsible. Chromosomal abnormalities and Y microdeletions in the azoospermia factor (AZF) region are known to be associated with spermatogenetic failure. In the present study, 289 patients with primary male infertility because of spermatogenetic failure were studied in order to highlight the molecular background of male infertility in Kuwait, and to avoid the possibility of transmission of any microdeletions/chromosomal aberrations to offspring via intracytoplasmic sperm injection (ICSI). Of the 289 infertile men, 23 patients (8%) had chromosomal aberration in the form of Klinefelter syndrome/variant (16/23; 69.6%), XYY syndrome (3/23; 13%), XX male syndrome (2/23; 8.7%), 45,X/46X, i(Yp)(1/23; 4.4%) and 45,XY, t(9;22) (1/23;4.4%). Y-chromosome microdeletion in the AZFb and AZFc regions were detected in 7/266 cases (2.6%). Testicular biopsy was carried out in 31 azoospermic patients, of whom five men had Sertoli-cell only syndrome, while 26 patients had spermatogenic arrest. In conclusion, this study showed that the frequency of both chromosomal anomalies and Y microdeletions were found in 10.4% of the infertile men. The potential risk of transmitting these genetic disorders to offspring provides a rationale for screening infertile men prior to ICSI.

Teletherapeutic drug administration by long distance closed-loop control of propofol.

BACKGROUND: The objective of this pilot study was to investigate the feasibility of an EEG-controlled closed-loop administration of propofol over a long distance of about 200 km. METHODS: We performed a teletherapeutic propofol infusion during total intravenous anaesthesia with propofol in 11 patients undergoing general surgery. The teletherapeutic system consisted of a computer at the patient site in Munich and a computer at the control site in Erlangen, which were connected via the internet through a virtual private network. The patient's EEG signal was sent to the control site computer, where the median frequency (MEF) of the EEG power spectrum was calculated. The propofol infusion, determined by a model-based adaptive feedback algorithm to maintain a MEF of 1.5 to 2 Hz, was sent to the patient site computer connected to the infusion pump. The quality of the control was assessed by the performance error defined as the percentage deviation of the measured MEF from the set point and the necessity of interventions by the anaesthetist at the patient site. RESULTS: During closed-loop administration of propofol [83 (52) min] the median performance error of the system was - 4.6 (4.4)% and the median absolute performance error was 18.8 (5.7)%. From a total number of 10 905 transmitted EEG epochs, there were five epochs with transmission errors, without further consequences for drug control. In one patient, teletherapy was stopped because the internet connection was interrupted. CONCLUSIONS: Teletherapeutic drug administration could be realized over a longer distance. Further studies have to investigate the practicability and safety of teletherapeutic drug control in anaesthesia.

Stability of ochratoxin A (OTA) during processing and decaffeination in commercial roasted coffee beans.

The fate of ochratoxin A (OTA) during the processing of artificially contaminated green coffee beans, the effect of decaffeination on the production of OTA in green and roasted coffee beans, and the effect of caffeine on the growth and OTA production by Aspergillus ochraceus were studied. The data indicated that the roasting, milling and decoction (brewing and Turkish coffee making) processes caused different percentage reductions in OTA. Decaffeinated samples showed a significantly higher concentration of OTA production than the caffeinated ones. A significantly higher percentage of OTA was reduced when the decaffeination process was performed before roasting treatment. Caffeine at 1.0 and 2.0% concentrations completely prevented OTA production and completely inhibited A. ochraceus growth in YES medium after 3-21 days.

A morpho-etiological description of congenital limb anomalies.

BACKGROUND: Limb anomalies rank behind congenital heart disease as the most common birth defects observed in infants. More than 50 classifications for limb anomalies based on morphology and osseous anatomy have been drafted over the past 150 years. The present work aims to provide a concise summary of the most common congenital limb anomalies on a morpho-etiological basis. PATIENTS AND METHODS: In a retrospective study, 70 newborns with anomalies of the upper and/or lower limbs were ascertained through clinical examination, chromosomal analysis, skeletal surveys and other relevant investigations. RESULTS: Fetal causes of limb anomalies represented 55.8% of the cases in the form of 9 cases (12.9%) with chromosomal aberrations (trisomy 13, 18 and 21, duplication 13q and deletion 22q) and 30 cases (42.9%) with single gene disorders. An environmental etiology for limb anomalies was diagnosed in 11 cases (15.7%) as amniotic band disruption, monozygotic twin with abnormal circulation, vascular disruption (Poland sequence, sirenomelia and general vascular disruption) and an infant with a diabetic mother. Twenty cases (28.5%) had limb anomalies as part of sporadic syndromes of unknown etiology. CONCLUSIONS: The morpho-etiological work-up of limb anomalies adopted in the present study is valuable for detecting the cause of the anomaly and is crucial for its prevention. Prevention can be achieved by proper genetic counseling, which includes recurrence risk estimation and prenatal diagnosis.

Fragile X syndrome: a clinico-genetic study of mentally retarded patients in Kuwait.

In a prospective study in Kuwait, 182 mentally retarded male patients who fulfilled 5 or more clinical criteria of fragile X syndrome were screened using polymerase chain reaction (PCR) testing. Twenty patients (11%) were highly suspected of having fragile X syndrome due to mutation at the FRAXA locus; none had mutation at the FRAXE locus. Of these, 11 (55%) were confirmed fragile-X-positive by both cytogenetic and PCR techniques. The most frequent clinical features were: prominent forehead, high arched palate, hyperextensible joints, long ears, prominent jaw, height > 10th centile and attention-deficit hyperactivity. Less common were avoidance of eye contact (45%), autism (45%) and seizures (30%). Large testes were found in 55% of cases. Pre-pubertal and post-pubertal clinical criteria were different.

Fragile X syndrome: a clinico-genetic study of mentally retarded patients in Kuwait

In a prospective study in Kuwait, 182 mentally retarded male patients who fulfilled 5 or more clinical criteria of fragile X syndrome were screened using polymerase chain reaction [PCR] testing. Twenty patients [11%] were highly suspected of having fragile X syndrome due to mutation at the FRAXA locus; none had mutation at the FRAXE locus. Of these, 11 [55%] were confirmed fragile-X-positive by both cytogenetic and PCR techniques. The most frequent clinical features were: prominent forehead, high arched palate, hyperextensible joints, long ears, prominent jaw, height > 10th centile and attention-deficit hyperactivity. Less common were avoidance of eye contact [45%], autism [45%] and seizures [30%]. Large testes were found in 55% of cases. Pre-pubertal and post-pubertal clinical criteria were different

A simple analysis of gene expression and variability in gene arrays based on repeated observations.

BACKGROUND AND AIM: At the present time there is an explosion of research in the area of gene arrays, and their application for detection of genes related to disease as well as its therapeutic manipulation. However, as individual arrays are expensive, comparisons of gene expression are often not repeated. In the current study, gene array experiments were repeated multiple times in order to understand the variability associated with measurements of gene expression. By focusing upon the pharmacologically important target of prostate cancer cell detachment, the current study employed multiple repeats of gene array experiments. This was used as a model system to demonstrate the utility of the experimental approach and statistical methods used. METHODS: To identify genes involved in detachment of prostate cancer cells (a prerequisite for metastases), we analyzed gene expression changes in metastatic variant PC3-M cells undergoing spontaneous detachment in culture. The data were interpreted using an elementary statistical approach. The between-experiment and within-repeated-observations variability in expression of 3582 genes possibly related to prostate cancer was also evaluated. RESULTS: One important gene related to prostate cell detachment was identified, based on the magnitude of its change in expression, as measured by a ratio of the expression after cell detachment and expression before detachment. On average, the variation between experiments was greater by about 30 to 40% than the variation between repeated observations. CONCLUSION: These findings have implications relating to the use of gene arrays to detect variance of gene expression, and should be taken into consideration in the prospective design of array experiments.

Is regional tonometry a reliable index of tissue oxygenation? A comparative study with conventional global monitoring.

This study was carried out on 30 critically ill patients admitted to the ICU of Farwania Hospital (Kuwait). All patients had clinical evidence of organ dysfunction or impending multiple organ failure. The severity of their pathology on admission was assessed according to the APACHE II score. The study of each patient began after inserting the pulmonary artery catheter. The prospectively defined end-point of the study was the removal of the pulmonary artery catheter (72 hours) or death of the patient with the catheter in situ. The aim of the study was to determine the sensitivity and specificity of the intra-gastric mucosal pH (pHi) and other derived data in assessing the adequacy of tissue oxygenation, guiding therapy and prediction outcome. The results showed that pHi, pHa-Hi and PaCO2-PO2regional (reg) gradients were the most sensitive indices of tissue oxygenation and predictors of outcome. The mortality rate increased when pHi, PaCO2-PCO2reg and pHa-pHi gradients were < 7.3, > 10 mm Hg and < 0.2 respectively. The derived variables obtained by invasive monitoring like base deficit (BD), lactate concentration in mixed venous blood (Lmv) and oxygn uptake index (O2 UI) were valuable adjunct indices of tissue oxygenation. The risk ofmortality increased whten the BD was > -5.5 +/- 1.2 meq.L-1, Lmv was > 4.5 +/- 1.2 mmol.L-1, and O2UI was < 100 +/- 6 ml.min-1.m-2. We recommend the use of gastric tonometry in routine ICU clinical practice.

Anxiety among school age children suffering from asthma.

The aim of the present work was to study anxiety among school age students suffering from asthma. The study was conducted on a total number of 146 asthmatic preparatory school students, attending the asthma clinic in Sporting Students' Hospital in Alexandria Governorate. The study was performed during the period from June to September 1997. A matching control of 223 non-asthmatic students from the preparatory school in the East educational zone in Alexandria Governorate were also included in the study. The study was carried out through a cross-sectional approach. A structured self-administered questionnaire was used to collect data about, the general characteristics of the sample, interpersonal and inter-parental relationships, school performance and the attitude and behavior of mothers towards their asthmatic children. The Arabic version of State-Trait Anxiety Inventory (STAI) was used to identify children with anxiety state. The present result revealed that 24.7% of the asthmatic students were anxious, with a higher preponderance among boys than girls (26.6%, 21.2%, respectively). Bad interpersonal and inter-parental relationships had increased the risk of occurrence of anxiety state among asthmatic children. Also, poor scholastic achievement was more encountered among asthmatics who had anxiety. The development of asthma education programs to increase parents', children's and teachers' awareness of asthma symptoms and asthma trigger events was recommended.

Trisomy 18 in Kuwait.

BACKGROUND: Trisomy 18 (Edwards' syndrome, T18) is the second most common trisomy in man. We describe 118 children with regular T18 who were ascertained clinically and cytogenetically in the Kuwait Medical Genetics Centre during 1980-1997. METHODS: Ascertainment of T18 cases was performed shortly after birth. Chromosomal studies were carried out in addition to other relevant investigations. To investigate the factors associated with T18, a case-control study was carried out with 131 normal healthy newborns. Studied factors included maternal and paternal age, birth order, abortion, associated malformation, and survival. Multiple logistic regression analysis was used to adjust for confounding between variables. RESULTS: There was a preponderance of females among T18 cases (female:male ratio 2.1:1). The majority of T18 cases (53%) died before the second week of life. The most common associated anomalies were: congenital heart (38.1%) and gastrointestinal (25.4%). Multiplicity of malformations was also observed. Significant seasonal variation in T18 cases was detected with a peak in spring. Of the 118 T18 cases, 59 were delivered during 1994-1997 (average overall T18 birth prevalence rate 8.95 per 10 000 live births [95% CI: 6.66-11.23]). Concerning maternal age, 30.5% of the T18 cases' mothers were > or =35 years compared to 10.7% in the control group. The difference was statistically significant, P = 0.002. Logistic regression analysis showed that maternal age >30 years was a significant risk factor for T18, after adjusting for confounding with paternal age. Paternal age and abortion were not found to be significant risk factors. CONCLUSION: Trisomy 18 birth prevalence rate is high in Kuwait with advanced maternal age as a significant risk factor.

PIP: This paper describes associated factors of trisomy 18 (T18) or Edwards' syndrome among infants in Kuwait. A case control study of 131 normal newborn controls was undertaken. The study included information about gender, maternal age, paternal age, birth order, reproductive history, consanguinity, survival, and associated anomalies. Results showed a preponderance of females among T18 cases (female/male ratio, 2.1:1). The difference between the T18-case mothers and the control-group mothers was statistically significant (P = 0.002); however, there was no significant difference with regard to paternal age. The logistic regression analysis showed that the odds ratio for 2 abortions with reference to (0/1) abortion was 1.086, which is statistically significant as a risk for T18. The majority of children with T18 died before the second week of life. With regard to malformations, the most common associated anomalies were congenital heart and gastrointestinal abnormalities. Thus, the prevalence of T18 is high in Kuwait, with advanced maternal age as a significant risk factor.

Clustering of trisomy 18 in Kuwait: Genetic predisposition or environmental?

BACKGROUND: This study describes 59 newborns with regular trisomy 18 (EdwardsA centAA syndrome, T18) who were ascertained clinically and cytogenetically at the Kuwait Medical Genetic Centre from 1994 to 1997, out of 118 T18 cases identified from 1980 to 1997. MATERIALS AND METHODS: T18 cases were ascertained clinically and cytogenetically shortly after birth. In addition to assessing the T18 birth prevalence rate and confidence limits during the years 1994-1997, we investigated the possible etiological factors by a case-control study with normal healthy newborns. Studied factors included gender, parental age, birth order, abortion, clinical variables (presentation, amniotic fluid and mode of delivery), and survival. RESULTS: The average T18 birth prevalence rate during the period was 8.95 per 10,000 live births (95% confidence limits 6.66-11.23). The T18 cases were mostly females, with a male:female ratio of 1:2.1, and the majority (53%) died before the second week of life. Maternal age above 30 years was found to be a significant factor for T18. CONCLUSION: This high T18 birth prevalence rate suggests clustering of T18 in the highly inbred population of Kuwait. Such clustering may indicate a possible environmental, and to a lesser extent, genetic predisposition to aneuploidy nondisjunction.

Prevention of maternal and developmental toxicity in rats via dietary inclusion of common aflatoxin sorbents: potential for hidden risks.

In earlier work, we have reported that a phyllosilicate clay (HSCAS or NovaSil) can tightly and selectively bind the aflatoxins in vitro and in vivo. Since then, a variety of untested clay and zeolitic minerals have been added to poultry and livestock feeds as potential "aflatoxin binders." However, the efficacy and safety of these products have not been determined. A common zeolite that has been frequently added to animal feed is clinoptilolite. Our objectives in this study were twofold: (1) to utilize the pregnant rat as an in vivo model to compare the potential of HSCAS and clinoptilolite to prevent the developmental toxicity of aflatoxin B1 (AfB1), and (2) to determine the effect of these two sorbents on the metabolism and bioavailability of AfB1. Clay and zeolitic minerals (HSCAS or clinoptilolite) were added to the diet at a level of 0.5% (w/w) and fed to pregnant Sprague-Dawley rats throughout pregnancy (i.e., day 0 to 20). Treatment groups (HSCAS or clinoptilolite) alone and in combination with AfB1 were exposed to sorbents in the feed as well as by gavage. Untreated and AfB1 control animals were fed the basal diet without added sorbent. Between gestation days 6 and 13, animals maintained on diets containing sorbent were gavaged with corn oil in combination with an amount of the respective sorbent equivalent to 0.5% of the estimated maximum daily intake of feed. Animals receiving AfB1 were dosed orally (between days 6 and 13) with AfB1 (2 mg/kg body wt) either alone or concomitantly with a similar quantity of the respective sorbent. Evaluations of toxicity were performed on day 20. These included: maternal (mortality, body weights, feed intake, and litter weights), developmental (embryonic resorptions and fetal body weights), and histological (maternal livers and kidneys). Sorbents alone were not toxic; AfB1 alone and with clinoptilolite resulted in significant maternal and developmental toxicity. Animals treated with HSCAS (plus AfB1) were comparable to controls. Importantly, clinoptilolite (plus AfB1) resulted in severe maternal liver lesions (more severe than AfB1 alone), suggesting that this zeolite may interact with dietary components that modulate aflatoxicosis. In metabolism studies, adult male Sprague-Dawley rats, maintained on diets containing 0.5% (w/w) HSCAS or clinoptilolite, were dosed orally with 2.0 mg AfB1/kg body wt. The concentration of the major urinary metabolite (AfM1) was considerably decreased in the presence of HSCAS. These results suggest that the mechanism of protection of AfB1-induced maternal and developmental toxicities in the rat may involve adsorption and reduction of AfB1 bioavailability in vivo. Importantly, this study demonstrates the potential for significant hidden risks associated with the inclusion of nonselective aflatoxin binders in feeds. Aflatoxin sorbents should be rigorously tested individually and thoroughly characterized in vivo, paying particular attention to their effectiveness and safety in sensitive animal models and their potential for deleterious interactions.

Prevention of post-operative nausea and vomiting following laparoscopic surgery--ephedrine vs propofol.

Postoperative nausea and vomiting (PONV) are relatively common troublesome distressing symptoms. The incidence is reported to be as high as 20-51%. Ninety adult ASA I and II patients scheduled for laparoscopic gynecological or surgical interventions, were randomly and equally assigned to one of the three groups in the immediate postoperative period: Group 1 received 0.1 ml.kg(-1) normal saline intravenously, while Group 2 received 0.5 mg.kg(-1) ephedrine intramuscularly and Group 3 received 0.25 mg.kg(-1) propofol intravenously as preventive antiemetic therapy. Sixty-six, 33 and 50 percent of patients experienced nausea and vomiting syndrome in Group 1, 2 and 3 respectively. Both ephedrine and propofol proved to have antiemetic properties. Ephedrine treated group of patient had significant less emetic score than propofol. No significant hemodynamic changes were recorded in both groups.