Stability of ceftazidime in normal saline solution after exposure to light.

Bactericidal activity of ceftazidime is determined by the time that concentrations in tissue and serum are above the MIC for the pathogens during the dosing interval. Thus, the most effective mode of administration of ceftazidime is continuous infusion. However, this agent is light sensitive which may result in instability when administered by this method without protection from light. Until now we have had no data to demonstrate the stability of this drug during continuous infusion. Therefore, the objective of this study was to provide such data. One gram of ceftazidime was mixed with 1,000 ml normal saline and exposed to two 36 watt fluorescence lights for 24 hours. The distance between ceftazidime solution and light source was 1 meter. Twenty samples (1 g-ceftazidime in normal saline) solution were evaluated. The mean ceftazidime concentrations in normal saline solution were decreased by only 1.69%, 4.44% and 7.19% after 6, 12 and 24 hours after exposure to light, respectively. Therefore, we conclude that the reduction of drug concentration was not considered to be significantly high, and this agent can be administered by continuous infusion.

A clinical checklist for fragile X syndrome: screening of Thai boys with developmental delay of unknown cause.

The aim of this study was to determine a cost-effective clinical checklist for fragile X syndrome (FXS) screening in a Thai male pediatric population with developmental delay of unknown cause. We studied 179 non-FXS male patients and 27 FXS patients from 18 families (age < or = 15 years). A six-item clinical checklist was used including family history (FH), long and narrow face (F), prominent and large ears (E), attention deficit/hyperactivity (AH), autistic-like behavior (AT) and testicular volume (T). These were scored as 0 if absent, 1 if borderline, and 2 if present. All patients were tested by using PCR and/or southern blot for the FMR1 gene. We used a logistic regression model from a computer program to analyze the data (Stata, version 5.0). We used logistic regression with cluster in the same family (average score) to eliminate bias from the related FXS cases. We found that a five-item checklist, 2FH + F + 0.5E + 2AH + T = total score, was the best model. When we used this clinical checklist with a threshold of total score of 4, 78.7 per cent of the screened cases with total scores < or = 4 could be eliminated as negative cases. In addition, all positive FXS cases had total scores > 4. We propose this five-item model for FXS screening in clinical pediatric practice, particularly from Asian population settings.

Establishing gas chromatography-mass spectrometry to diagnose organic acidemias in Thailand.

Disorders of organic acid metabolism are a group of disorders which has long been ignored by majority of Thai physicians. Part of this is due to lack of laboratories in Thailand to verify the diagnosis of the disorders. We have recently developed a technique to qualitatively analyze organic acids utilizing Gas Chromatography-Mass Spectrometry (GC-MS). Eight patients in four families were successfully identified as having organic acidemias (OA) by this method. Two families had methylmalonic acidemia, one had propionic acidemia, and the other had 3-methylcrotonyl CoA carboxylase deficiency. To our knowledge, this is the first laboratory in Thailand being able to use GC-MS to diagnose OA. Availability of a laboratory in Thailand and affordability of the test are expected to result in earlier diagnosis and identification of more cases of OA in Southeast Asian countries. Consequently, prompt and proper treatment can be anticipated which should lead to better prognosis for patients with this group of disorder.

Pseudohypoaldosteronism: mineralocorticoid unresponsiveness syndrome.

We described a 10 day old boy who presented with hyponatremia, hyperkalemia, and metabolic acidosis. Therapeutic treatment with exogenous glucocorticoid and mineralocorticoid for 8 months failed to correct the electrolyte abnormalities. The elevated serum cortisol up to 44.34 micrograms/dl along with the absence of skin hyperpigmentation excluded defects in the glucocorticoid pathway. Pseudohypoaldosteronism was diagnosed on the basis of hyponatremia, severe urinary salt loss despite the markedly elevated serum aldosterone up to 6,500 pg/ml (normal range 50-800 pg/ml). The patient responded very well to oral salt supplementation and cation exchange resin therapy shown by normal physical growth and normal levels of serum electrolytes.

The usefulness of serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) for evaluation of children with short stature.

The diagnostic value of serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) was studied in 24 growth hormone deficient (GHD) and 36 normal variant short stature (NVSS) children. The serum IGF-1 and IGFBP-3 concentrations were markedly below the 5th centile for chronological age in all 24 GHD children, but were in the low normal range for age in most of the NVSS children. The concentrations of IGF-1 and IGFBP-3 significantly correlated with peak GH concentration, height age, and bone age. To account for the age- and sex-dependency, IGF-1 and IGFBP-3 levels were transformed to standard deviation score (SDS). Using the -2 SDS as a cut-off level to differentiate between GHD and NVSS, the diagnostic value of IGF, as well as IGFBP-3, showed sensitivity 100 per cent, specificity 66.7 per cent, and accuracy 80 per cent. The combined use of IGF-1 and IGFBP-3 < -2 SDS improved the diagnostic value with sensitivity 100 per cent, specificity 77.8 per cent, and accuracy 86.7 per cent. We concluded that the serum concentrations of IGF-1 and IGFBP-3 could reflect endogenous GH secretion and could be used as a screening evaluation of GH status in short children.

An identical neo-mutation in the thyroid hormone receptor beta gene (A317T) in 2 unrelated Thai families with resistance to thyroid hormone.

We reported two unrelated Thai girls with resistance to thyroid hormone. The affected patients presented with goiter and no other stigmata of hyperthyroidism. Their serum T4, T3, free T4 and free T3 concentrations were high and they had normal levels of TSH. The affected girl in family 1 was treated with an antithyroid drug for 1-9/12 years. The affected girl in family 2 was only observed her thyroid function tests. TRH test showed normal TSH response in both girls. Analysis of the thyroid hormone receptor beta gene of both affected girls revealed the same missense mutation, changing the guanine in nucleotide 1234 to an adenine which results in the replacement of the normal alanine (GCT) with a threonine (ACT) at codon 317. Two proposita were heterozygous, and this mutation was not present in their parents compatible with a neo-mutation.

Hypophosphatasia: the importance of alkaline phosphatase in bone mineralization.

The authors describe a neonate who was diagnosed with "perinatal hypophosphatasia". The clinical manifestations in this patient were small head size, soft calvarium (caput membranaceum), and short bowing forearms and legs. Laboratory investigations revealed hypercalcemia at 12.7 mg/dl, hyperphosphatemia 8.6 mg/dl, and extremely low alkaline phosphatase 0 unit/L. Roentgenographic studies of the skull showed calcification only at frontal bone and base of the skull. Spines were small and flattened. Long bones were hypomineralized and deformed. The functions of alkaline phosphatase to bone development and mineralization were reviewed. Because perinatal hypophosphatasia is a fatal condition and inherited as an autosomal recessive pattern, prenatal diagnosis is necessary. The most reliable and suitable method in our facility is serial ultrasonography from which the diagnosis can be made by the second trimester.

Serum insulin-like growth factor-1 (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) in healthy Thai children and adolescents: relation to height, weight, and body mass index.

The objective of this study was to evaluate the correlation between serum concentrations of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and growth parameters (height, weight, and body mass index) in 260 healthy children and adolescents aged 5-20 years. The subjects were divided into 2 groups according to the age achieving final height. Group 1 included children with active growth consisting of girls aged under 14 years (N = 80) and boys aged under 16 years (n = 74). Group 2 included adolescents who achieved final height consisting of females aged at and over 14 years (n = 82), and males aged at and over 16 years (n = 24). In group 1, the serum concentrations of IGF-1 and IGFBP-3 were significantly positive correlated with all growth parameters. In group 2, although the correlation was insignificant, the concentrations of IGF-1 and IGFBP-3 seemed to be greater in individuals who were relatively taller and had lean body mass than those who were relatively short and over average body mass.

Growth patterns of low-birth-weight infants: 2-year longitudinal study.

A 2 year longitudinal study of the growth of 147 low birthweight (LBW) < 2,500 g infants who had no known factors disturbing growth was conducted. The infants were divided into 6 groups according to birthweight and maturity: group 1--appropriate for gestational age (AGA) with birthweight < 1,500 g (n = 18); group 2--AGA 1,500-1,999 g (n = 41); group 3--AGA 2,000-2,499 g (n = 26); group 4--small for gestational age (SGA) < 1,500 g (n = 5); group 5--SGA 1,500-1,999 g (n = 20); group 6--SGA 2,000-2,499 g (n = 37). The control group consisted of 149 normal birthweight (> 2,500 g) infants. Weight, height, and head circumference were measured at birth, 2, 4, 6, 9, 12, 18, and 24 months postnatally and recorded in standard deviation score (SDS). All groups showed catch-up growth in the first 6 months. At 2 years old, all infants were above -2 SDS. However, the SGA infants with birthweight < 1,500 g were significantly lighter (-0.9 SDS, p = 0.003), shorter (-0.6 SDS, p = 0.001) and had smaller head size (-0.65 SDS, p = 0.027) whereas, the other groups were not different compared to the control group. We also compared those LBW infants who, at 2 years of age, weighed below -1 SDS to those who weighed above -1 SDS and found no significant difference in familial income, parental education, nursing care or parental height. We concluded that with adequate nutritional intake and nursing care, LBW infants have the potential for good catch-up growth. For the SGA infants with birthweight < 1,500 g, although they showed good catch-up growth, they still remained smaller than their peers at 2 years of age.

Serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in healthy Thai children and adolescents: relation to age, sex, and stage of puberty.

The authors studied the serum concentrations of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) in 260 healthy children and adolescents (115 males, 145 females) aged 5-20 years. The subjects were divided into 12 groups according to age and sex. The serum IGF-1 and IGFBP-3 concentrations increased with age and peaked at age 13-15 years in males, and 11-13 years in females. After the peak concentration, IGF-1 and IGFBP-3 levels declined significantly in males, but were still high in females. Comparing between sexes, the concentrations of IGF-1 and IGFBP-3 were greater in females than males in all age groups. However, when subjects were divided according to the stage of puberty, the different concentrations between sexes were not significant, except for children within Tanner stage V where concentrations of IGF-1 and IGFBP-3 were significantly greater in females than males. Multiple regression analysis demonstrated the age, sex, and stage of puberty-dependent of IGF-1 concentration, and only the age and sex-dependent of IGFBP-3 concentration.

The pharmacokinetics of oral rifampicin in AIDS patients.

Previous studies in AIDS patients have shown that the peak serum concentration of rifampicin at 2 hours after administration are below normal ranges. These may be due to malabsorption of the drug resulting in therapeutic failure. However, there is no published data to demonstrate the pharmacokinetics of rifampicin in these AIDS patients. Therefore, the aim of this study was to provide such data. Eight AIDS patients with tuberculosis participated in this study. All patients were scheduled to receive oral rifampicin 600 mg once daily in the morning on an empty stomach. Rifampicin pharmacokinetics were studied on day 14. The mean Cmax was 9.81 +/- 4.41 ug/ml. The mean Tmax was 2.25 +/- 0.71 h. The mean AUC0-24 was 60.25 +/- 36.88 ug.h/ml. The results of our study did not confirm the previous studies. The absorption of rifampicin in most of our AIDS patients were not reduced and delayed. Therefore, rifampicin dosage adjustment for Thai patients may not be necessary.

Amphotericin B with or without flucytosine followed by fluconazole as primary therapy for cryptococcal meningitis in patients with AIDS.

Eighteen consecutive AIDS patients with a first episode of cryptococcal meningitis were enrolled in the study to evaluate the efficacy and tolerability of amphotericin B with or without flucytosine followed by fluconazole as primary therapy for cryptococcal meningitis in patients with AIDS. The treatment consisted of intravenous amphotericin B 0.6 mg/kg daily with or without flucytosine (150 mg/kg d in four divided doses) for 2 weeks which was then followed by oral fluconazole 400 mg daily for 8 weeks. After completion of primary therapy, all patients received a maintenance dose of oral fluconazole 200 mg daily. The primary therapy was successful in 17 (94%) of the 18 patients. The median length of time to the first negative cerebrospinal fluid culture for Cryptococcus neoformans in the 17 patients with successful treatment was 3 (range 2 to 6) weeks. No patient had to discontinue the treatment due to adverse drug reactions. During a mean observation period of 26.94 weeks, no relapse case was documented among the 17 patients. Our results indicate that this regimen as primary therapy for cryptococcal meningitis in AIDS patients is effective and well tolerated.

P450scc deficiency (congenital lipoid adrenal hyperplasia): first reported case in Thailand and literature review.

A male infant presented with hyponatremia, hyperkalemia, generalized skin hyperpigmentation, and female type external genitalia. These clinical findings were compatible with mineralocorticoid, glucocorticoid and androgen insufficiency. Serum cortisol, progesterone and testosterone levels were extremely low after ACTH stimulation test, suggestive of defect in all of the adrenal steroidogenesis. Computed tomography demonstrated enlarged adrenal glands. The diagnosis of P450scc deficiency or lipoid congenital adrenal hyperplasia was based on all these characteristics. Physiologic replacement therapy with hydrocortisone and 9 alpha-fluorocortisol were effective and the patient achieved normal growth. The clinical characteristics, differential diagnoses, and prenatal diagnosis are discussed and reviewed.

Goiter in Thai schoolchildren: study in Hat Yai, southern Thailand.

Examination for goiter was performed in 6,035 schoolchildren (2,899 girls, 3,136 boys), aged 8-17 years, from primary and secondary schools in Hat-Yai municipality, Songkhla province. Goiter was detected in 355 children (combined prevalence 6%; 232 or 8% in girls, 123 or 4% in boys). Of the 355 children with goiter, 214 (60%; 148 girls, 66 boys) participated in the study, and had blood drawn for free thyroxine (FT4), triiodothyronine (T3), thyroid stimulating hormone (TSH), and thyroid antibodies. All had urine collected for iodine excretion. The diagnoses of goiter were as follows: simple goiter in 192 (89.8%; 129 girls, 63 boys); juvenile autoimmune thyroiditis in 18 (8.4%; 16 girls, 2 boys); Graves' disease in 2 girls (0.9%); thyroid adenoma in 1 boy (0.45%), and ectopic thyroid in 1 girl (0.45%). Acquired hypothyroidism was found in 4 out of 18 children with juvenile autoimmune thyroiditis (22.2%). Iodine deficiency disorder was not evident in children examined shown by high urinary iodine excretion of more than 50 mcg/gm creatinine (mean 298, range 70-630). In conclusion, simple goiter is a common occurrence in children and adolescents in Southern Thailand. Juvenile autoimmune thyroiditis should be identified and differentiated from simple goiter as it is the most common cause of acquired hypothyroidism. Iodine deficiency is not evident in Southern Thailand, at least in the urban areas of a large city.

Idiopathic hyperprolactinemia in a 15-year-old boy: a case report and literature review.

A 15-year-old boy with idiopathic hyperprolactinemia is described. He was markedly obese, in early puberty, and had gynecomastia and galactorrhea. Serum prolactin level was high, up to 220 pg/ml. Thyroid function test was normal. Idiopathic hyperprolactinemia was diagnosed on the basis of elevated prolactin level, and no demonstrable pituitary tumor was revealed by computerized tomography brain scan and magnetic resonance imaging. Bromocriptine was started initially at the dose 2.5 mg/day, then increased to 7.5 mg/day. Galactorrhea disappeared and prolactin level decreased to < 10 ng/ml. A review of the literature indicates that idiopathic hyperprolactinemia in adolescent males is extremely rare. To our knowledge, this patient is the youngest reported case of hyperprolactinemia in Thailand.

Zellweger syndrome: first reported case in Thailand and literature review.

We describe an infant boy with facial dysmorphism, profound hypotonia, psychomotor retardation, seizure and hepatomegaly. Biochemical study revealed elevation of very long chain fatty acids and pipecolic acid, consistent with peroxisomal disorder. He died at the age of 4 months. Electron microscopic study demonstrated decreased amounts of peroxisomes in liver and kidneys. The clinical characteristic, accompanied the biochemical and microscopic findings led to the diagnosis of Zellweger syndrome. The recognition of this syndrome is important since it is a fatal disease. The pattern of inheritance is autosomal recessive, hence genetic counseling is necessary. We emphasize that peroxisomal disorder should be included in the differential diagnosis in patients with infantile hypotonia. This patient is the first reported case of Zellweger syndrome in Thailand.

An infant with Down-Turner double aneuploidy: a case report and literature review.

The case of an 8 month-old female infant with non-mosaic Down-Turner double aneuploidy is reported. She had Down facies without stigmata of Turner syndrome. A review of 22 previous reported cases revealed mosaicism in all cases, either 21 mosaic or X mosaic. Our patients is the first reported case of non-mosaic trisomy 21-monosomy X polysyndrome in Thailand.

Multiple endocrine neoplasia type IIb: a case report.

We reported a 14-year-old boy who had had multiple thyroid nodules for 4 yrs. Physical examination revealed marfanoid habitus, coarse facies with thick lips and prominent jaw. Mucosal neuromas were present on the buccal mucosa, tongue and upper eyelids. Thyroid scan demonstrated multiple, cold nodules and medullary thyroid carcinoma was confirmed by pathological examination. He was normotensive and his 24 hrs urinary vanillyl mandelic acid was in the normal range. Computerized tomography demonstrated normal adrenal glands. Multiple endocrine neoplasia type IIb (MEN IIb) was diagnosed by the appearance of typical phenotypic features, multiple mucosal neuromas and medullary thyroid carcinoma. The scarcity of such reports in children and the importance of early recognition of this disorder prompted us to describe this patient.

Edwardsiella tarda: a causative agent in human infections.

In a retrospective study 45 specimens of E. tarda infection from 44 adult cases at Songklanagarind Hospital during February 1982 to March 1989 were reviewed. There were 24 males and 20 females, with a mean age of 48.20 years. Nearly all of E. tarda were isolated from extraintestinal sources, especially pus and urine and most of them were subsequently found to be nosocomial-acquired infections. About half were polomicrobial infections of E. tarda and gram negative bacilli. Forty one patients were cured of the infection. Three cases died from bacteremia and serious underlying diseases.

Traumatic wound infection due to Bacillus cereus in an immunocompromised patient: a case report.

A young man recently responding to immunosuppressive therapy for acute myelocytic leukemia was admitted with fever and haemorrhagic blebs on both extremities after sustaining some scratch marks in a muddy pond. Gram stains of the hemorrhagic fluid in the blebs revealed many gram positive bacilli. B. cereus was identified from culture of tissue fluid. He did not respond to therapy despite bacteriological cure. Terminally, he developed Pseudomonas aeruginosa bacteremia and generalized bleeding.