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Background: The influence of child characteristics on warfarin dosing has been reported; however, there is no consensus on the nature and extent of this effect., Objectives: To investigate the impacts of the demographic and clinical characteristics of children on the warfarin dose required to achieve a therapeutic international normalization ratio (INR)., Methods: This retrospective cohort study included children aged 3 months to 14 years old who were prescribed warfarin for 3 months or longer with a "stable INR." The primary outcome was the total daily dose (TDD) and total weekly dose of warfarin required to achieve a therapeutic INR target., Results: We included 127 patients with a mean age of 7.7 ± 3.7 years and a median weight of 22 (IQR, 16-33) kg. Of the sample, 55 patients (43.3%) required a TDD of ≤0.1 mg/kg. The TDD for children younger than 5 years, 5 to 10 years, and older than 10 years were 0.14 ± 0.06 mg/kg, 0.12 ± 0.05 mg/kg, and 0.096 ± 0.04 mg/kg, respectively ( P  = .002). Overweight and obese children required a smaller TDD than normal-weight children: 0.09 ± 0.05 vs 0.13 ± 0.05 mg/kg ( P  = .004), which was similar for underweight children. A lower body surface area (<0.5 m 2 ) required a higher dose. All the other variables did not affect warfarin doses. The incidence of a subtherapeutic or supratherapeutic INR was independent of demographic or clinical variables., Conclusion: The study confirmed that the patient demographics affect the daily warfarin dose required to achieve the INR target. However, they do not have any predictive value for the incidence of out-of-range-INR., (© 2024 The Author(s).)

Most pharmaceutical peptides are supplied as acetate salts and the relative amount of acetate to peptide in the final product is one quality criterion required by regulatory agencies to approve the product for clinical use. The objective of the present study was to develop a validated LC-MS/MS method that allows the quantitative determination of the acetate content in pharmaceutical peptide preparations and simultaneous monitoring and collection of qualitative and quantitative information on the peptide during manufacture and in the final product. The method uses reversed phase C 18 -chromatography to elute the acetate ions under acidic conditions, pH 3, followed by post-column infusion of ammonium hydroxide 0.6M, methanolic solution (30:70) at a rate of 0.5mL/hr. The acetate ions were monitored in negative polarity mass spectrometry by pseudo multiple reaction monitoring (pseudo MRM) against 1, 2- 13 C labelled acetate, the internal standard used in the method. The method was linear for acetate concentrations between 0.4 and 25μg/mL with a coefficient of determination (r 2 ) equal to 0.9999. The minimum level of detection and minimum level of quantification were at 0.06μg/mL and 0.18μg/mL respectively. Accuracy of the method was judged by determining the acetate content in a commercial product of the peptide pharmaceutical tetracosactide (TCS) and parallel comparison to the amounts determined by a reversed phase HPLC method with detection at a wavelength of 210nm. The amounts determined by the two methods were in agreement with a RSD that was less than 2%. Additional confirmation of method accuracy was determined by spiking the pharmaceutical peptide with varying amounts of acetate. The recoveries ranged on average between 101 and 102% for the spiked amounts. Accuracy was also determined by calculating the percentage relative error of the predicted to actual acetate concentration in quality controls and was determined to be less than 5%. The LC-MS/MS method was precise with an intra- and inter-day RSD of less than 5%. The standard solutions were stable for at least one month when kept frozen at -80°C with no loss in response and an inter-day RSD of less than 5%. The method was applied to quantify the acetate content in the clinically available product of TCS and to simultaneously evaluate the average peptide molecular weight and detect known impurities by switching from negative polarity MRM analysis to positive polarity MS analysis following the elution of the acetate peak. The method reported herein should corroborate quantitative determinations of the acetate content in pharmaceuticals by the traditional compendial HPLC method., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background/aims: Success of colorectal cancer (CRC) screening is dependent in part on the proportion of uptake by the targeted population. We aimed in this study to identify factors that were associated with willingness to undergo CRC screening based on the health belief model (HBM)., Patients and Methods: This was a cross-sectional study among citizens of Riyadh, Saudi Arabia. Demographic data collected included gender, age, education, marital status, employment status, a history of CRC in the family or knowing a friend with CRC, as well as income. A questionnaire was developed in Arabic based on the HBM and included enquiries on knowledge about CRC symptoms and risk factors, types of CRC screening tests, perceived risk of CRC, previously undergoing CRC screening, intent to undergo CRC screening, perceived barriers to CRC screening, perceived severity of CRC, as well as attitudes toward CRC and its screening., Results: Five hundred participants were included. The mean age was 41.0 years (SD 10.7). Males were 50% and only 6.7% of those between 50 and 55 years of age had undergone CRC screening. Of those surveyed, 70.7% were willing to undergo CRC screening. Also, 70.5% thought that CRC is curable, 73.3% believed it was preventable, whereas 56.7% thought it was a fatal disease. Neither gender, level of education, occupation, income, marital status, nor general knowledge about CRC was found to be associated with the willingness to undergo CRC screening. Recognizing that colonoscopy was a screening test (OR 1.55, 95% CI; 1.04-2.29) was associated with a strong desire to undergo CRC screening while choosing a stool-based test was associated with not willing to undergo CRC screening (OR 0.59, 95%CI; 0.38-0.91)., Conclusion: We found that the majority of those interviewed were willing to undergo CRC screening and identified a number of barriers as well as potential areas that could be targeted in the promotion of CRC screening uptake if such a national program were to be implemented.

Objective: To examine the in vitro antimicrobial effect of a 20% Miswak extract against a mixture of Candida albicans (C. albicans) and Enterococcus faecalis (E. faecalis) using the dilution tube susceptibility test, which allows direct contact between the tested material and the microorganisms., Methods: The study samples were collected and processed between August 2009 and January 2010 in the College of Dentistry, King Saud University, Riyadh, Saudi Arabia. Each microorganism was obtained in a suspension and exposed to a 20% Miswak extract in plastic tissue culture clusters containing 24 wells. Six wells were used per group. The Miswak extract was incubated with the microorganisms for one, 6, and 24 hours., Results: This in vitro study showed that Miswak extract was an effective antifungal and antibacterial agent at all tested experimental time periods, except one hour exposure of a 20% Miswak extract to E. faecalis and a mixture of E. faecalis and C. albicans, which was ineffective in inhibiting their growth., Conclusion: Twenty percent Miswak extract is an effective antifungal and antibacterial agent against C. albicans and E. faecalis.

The clinical, biochemical, and neuroradiologic findings and clinical follow-up of seven patients with glutaric aciduria type II are reported. Three phenotypes of the disease are encountered: neonatal-onset form with congenital anomalies (two patients) or without congenital anomalies (three patients) and late-onset form (two patients). The neonatal-onset form presents as an overwhelming illness, with severe hypoglycemia and metabolic acidosis leading to rapid death. Frequently it is associated with perinatal energy deprivation, a neonate with low birth weight and prematurity. The late-onset form presents with intermittent episodes of vomiting, hypoglycemia, and acidosis especially after meals rich in fat and/or proteins. All parents are consanguineous and have a first- or second-degree relationship. Initially, in the two phenotypes with neonatal onset and during crisis in the late-onset phenotype, routine laboratory evaluation showed severe metabolic acidosis, with an increased anion gap, hypoglycemia without ketonuria, and disturbed liver function tests. In the majority of patients with neonatal-onset forms, the kidneys, liver, and at times the spleen are enlarged with an increased echogenic pattern; however, no hepatic or renal cysts are detected. Cardiomegaly is observed in most patients. The diagnosis can be easily and rapidly reached through tandem mass spectrometry study of the blood and can further be confirmed by gas chromatography/mass spectrometry analysis of the urine organic acids. In this report, the magnetic resonance imaging/computed tomography brain studies showed brain atrophy, white matter disease, and in one patient, fluid-filled cavities in the periventricular area and putamina. Fluorine-18-labeled 2-fluoro-2-deoxyglucose positron emission tomographic (FDG PET) brain studies in two patients with late-onset disease showed slightly decreased activity in the cerebral cortex in one and in the caudate nuclei in the other. Brain FDG PET scan and magnetic resonance spectroscopy were normal in one patient with neonatal-onset disease. All patients were treated with a diet low in fat and protein, oral riboflavin, and carnitine. The results were promising for the late-onset disease. Intravenous carnitine gave rewarding results in one patient with neonatal-onset disease.

We report a five-year-old boy with 4-hydroxybutyric aciduria. The child presented with global developmental delay, severe hypotonia and myoclonic seizures. The urine 4-hydroxybutyric acid was 1038 times that of normal, and other organic acids related to its further metabolism were also increased. Electroencephalography showed findings indicative of cerebral dysfunction. However, other neurophysiological studies were normal. Clinical improvement was observed after the administration of vigabatrin and dextromethorphan. Magnetic resonance imaging of the brain revealed cerebellar vermin atrophy and subtle white matter changes in the cerebral hemispheres. Fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomographic (FDG PET) scan of the brain showed a marked decrease in the cerebellar metabolism, probably related to atrophy of cerebellar vermis and secondary cerebellar deafferentation. FDG PET scan is found to be of value in the understanding and assessment of brain functional alterations. It may be useful in monitoring and optimizing treatment strategies of this rare disease.

A 2-year, 6-month-old Saudi male with infantile Krabbe's disease was studied with fluorine-18-labeled-2-fluoro-2-deoxyglucose positron emission tomography (FDG PET) scan. The patient presented with a gradual loss of developmental milestones, irritability, and crying. At the advanced stage of the disease, he developed tonic-clonic seizures and became a microcephalic, extremely irritable, blind, spastic quadriplegic child, with no deep tendon reflexes. Laboratory studies revealed normal blood chemistry, muscle enzymes, very long chain fatty acids, and acylcarnitines. No abnormal urinary organic acids were detected. The cerebrospinal fluid protein concentration was increased. Magnetic resonance imaging of the brain revealed mild brain atrophy and white matter disease mainly in the centrum semiovale. Electroretinography was normal; however, electroencephalography and visual-evoked potentials were abnormal. Peripheral nerve conduction studies documented a demyelinating neuropathic process. The FDG PET study of the brain demonstrated a marked decrease in the metabolism of the left cerebral cortex and no uptake in the caudate heads. Normal glucose uptake was observed in the thalami, lentiform nuclei, and cerebellum. The patient did not present for subsequent clinic visits and is presumed dead.

Objective: To evaluate the clinical, biochemical, neuroradiological, and neurophysiological findings of patients with X-linked adrenoleukodystrophy., Methods: Retrospective study evaluating the data of 10 X-linked adrenoleukodystrophy patients diagnosed at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Results: The common presenting symptoms were deterioration in school performance, vision and hearing, behavioral changes, and seizures. Eight patients survived 1-4 years and one patient 12 years after the initial presentation, while one patient expired. Six patients had the childhood form, 3 had the adolescent form and one had the adrenomyeloneuropathy form. Six are in an advanced stage of the disease and 3 have mild to moderate spasticity. All except 2 manifested moderate to severe dementia with variable degrees of visual loss. Decreased hearing and features of adrenal insufficiency were seen in 7 patients. Very long chain fatty acids were significantly increased in seven and mildly elevated in 2 patients, however the C26 to C22 ratio was increased in all. The characteristic high-signal intensity of parieto-occipital white matter on brain magnetic resonance imaging T2-weighted images was observed in all patients. Two patients had functional study of the brain, which showed hypometabolic activity in gray and white matter of the occipital lobes. Various neurophysiological abnormalities were detected. The response to different treatment modalities was not promising., Conclusion: The disease is more common than had been previously recognized due to phenotypic variability and a wide spectrum of presentations. This report describes various aspects of this disorder and emphasizes the importance of early identification and treatment of asymptomatic but biochemically affected individuals, since all current therapeutic approaches are disappointing if overt neurological abnormalities have been already developed.

The clinical, biochemical, pathological and neuroradiological findings of a 2-year-old Saudi boy with infantile G(M1) gangliosidosis are reported. The patient had a progressive neurologic deterioration, manifesting with developmental regression, sensorimotor and psychointellectual dysfunction and generalized spasticity that started at 4 months of age. Cherry-red macula, facial dysmorphia, hepatomegaly, exaggerated startle response to sounds, skeletal dysplasia, and vacuolated foamy lymphocytes that contain finely fibrillar material in addition to lamellar membranes and electron-dense rounded bodies were seen. MRI of the brain demonstrated mild diffuse brain atrophy and features of delayed dysmyelination and demyelination. Brain FDG PET scan revealed a mild decrease in the basal ganglia uptake, and moderate to severe decrease in thalamic and visual cortex uptake, and an area of increased glucose uptake in the left frontal lobe, probably representing an active seizure focus. The functional changes indicated by FDG PET scan and the structural abnormalities shown on MRI were found to be complementary in the imaging evaluation of infantile G(M1) gangliosidosis.

Pipecolic acid is a biochemical marker frequently detected in group 1 peroxisomal disorders (peroxisomal biogenesis disorders). Its presence, in addition to the constellation of particular phenotypic manifestations and pathologic findings, has led to its recent classification under disorders of peroxisomal biogenesis as a separate disease entity (hyperpipecolic acidemia or hyperpipecolatemia). The clinical, biochemical, and radiologic findings observed in three patients diagnosed with hyperpipecolic acidemia are reported.

We retrospectively reviewed clinical and biochemical data of four patients diagnosed with tyrosinaemia type II. Diagnosis was established by high plasma tyrosine and normal plasma phenylalanine levels using plasma high-pressure liquid chromatography and tandem mass spectrometry. All patients were mildly mentally retarded and had painful non-pruritic and hyperkeratotic plaques on the soles and palms. There were no ophthalmic symptoms. The patients dramatically responded clinically and biochemically to a diet restricted in tyrosine and phenylalanine.

The clinical manifestations of neonatal encephalopathies lack specificity and may present with predominantly seizures, hypotonia or coma. We have selected several examples of neonatal encephalopathies which are of special interest because of their genetic origin and present their clinical features, typical course and, when available, treatment.

The cases of three infants, two Saudi and one Bahraini, with methylenetetrahydrofolate reductase (MTHFR) deficiency are reported. They presented in the neonatal period with lethargy, poor feeding, hypotonia, and frequent apneas. Tandem mass spectrometry (MS/MS) of a blood spot indicated very low methionine level and of urine revealed high homocysteine. The diagnosis was confirmed by demonstrating severe deficiency of MTHFR in the cultured skin fibroblast. All patients were treated with folinic acid, vitamin B12, betaine, and methionine, with good initial response to the therapy. In two patients, the diagnosis was late and their disease was severe, resulting in neurological crippling. However, in the third patient, who was diagnosed and treated early, the current neurological status is normal. In her case, at 1 month of age, the brain FDG PET scan documented very faint cerebral and cerebellar cortical activities. After 5 months of intensive therapy, that included 200-600 mg/kg per day methionine, she had a dramatic clinical and biochemical recovery as well as a parallel improvement in FDG PET. Brain MR spectroscopy indicated normal neuronal glial and myelin markers for her age. We conclude that the functional changes confirmed by the FDG PET study were better correlated with the clinical course of the patient and adequately monitored the response to therapy. This disease warrants early detection through neonatal screening program, since the beneficial effect of early administration of adequate therapy with combined use of betaine and a high dose of methionine is rewarding and may be the treatment of choice for MTHFR deficiency.

We report a 2-year-old boy with ethylmalonic aciduria and vasculopathy syndrome evaluated by 18fluoro-2-deoxyglucose positron emission tomographic (18FDG PET) brain scan, with intense uptake of 18FDG in the caudate nucleus and putamen bilaterally but with no morphological changes on magnetic resonance imaging (MRI). A repeat 18FDG PET brain scan 1 year later showed a significant bilateral decreased uptake of glucose in the putamen and the head of the caudate nucleus as well as a decreased uptake in the frontal lobes. On MRI, there was atrophy and watershed infarcts in the basal ganglia, explaining the loss of glucose uptake. These results reflect a selective vulnerability of the basal ganglia, their functional derangement, and ultimate degeneration.