A randomized clinical trial of chlorhexidine in the maintenance of oral candidiasis-free period in HIV infection.

OBJECTIVE: To determine if chlorhexidine can be used as an intervention to prolong the time to relapse of oral candidiasis. SUBJECTS AND METHODS: A double-blinded randomized clinical trial was performed in 75 HIV/AIDS subjects with oral candidiasis. Clotrimazole troche was prescribed, and the subjects were re-examined every 2 weeks until the lesions were completely eradicated. The subjects were then randomly divided into two groups; 0.12% chlorhexidine (n = 37, aged 22-52 years, mean 34 years) and 0.9% normal saline (n = 38, aged 22-55 years, mean 38 years). They were re-examined every 2 weeks until the next episode was observed. RESULTS: The time to recurrence of oral candidiasis between the chlorhexidine and the saline group was not statistically significant (P > 0.05). The following variables were significantly associated with the time of recurrence; frequency of antifungal therapy (P = 0.011), total lymphocyte (P = 0.017), alcohol consumption (P = 0.043), and candidiasis on gingiva (P = 0.048). The subjects with lower lymphocyte showed shorter oral candidiasis-free periods (P = 0.034). CONCLUSIONS: Chlorhexidine showed a small but not statistically significant effect in maintenance of oral candidiasis-free period. This lack of significance may be due to the small sample size. Further study should be performed to better assess the size of the effect, or to confirm our findings.

Clinics in diagnostic imaging (112). Perinatal lethal hypophosphatasia (PLH).

A two-hour-old female infant presented with respiratory distress and short limbs. Neonatal radiographs showed micromelic dwarfism and generalised demineralisation, especially at the ribs, long bones of both forearms and both fibulae. The spine showed a flattened shape. All long bones showed metaphyseal irregularities and flaring. Normal serum calcium and elevated serum phosphorus were found, while serum alkaline phosphatase was markedly reduced. A diagnosis of perinatal lethal hypophosphatasia was made. The aetiology, clinical manifestations, radiographical findings, laboratory assays, prenatal diagnosis and treatment of hypophosphatasia are discussed.

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.

Effect of indinavir on the pharmacokinetics of rifampicin in HIV-infected patients.

Indinavir, an antiretroviral agent, has an influence on the pharmacokinetics of other drugs by acting as an inhibitor of cytochrome P450-mediated drug metabolism. The incidence of tuberculosis has increased dramatically in the past decade because of an epidemic of HIV infection. Rifampicin is still one of the most valuable drugs for the standard treatment of tuberculosis. The objective of this study was to investigate the effects of indinavir on the pharmacokinetics of rifampicin in man. Our study was conducted in eleven HIV-infected patients. All patients received a 600-mg single dose of oral rifampicin on day 1 and 15- and 800-mg oral indinavir three times a day from day 2 to day 15. Rifampicin pharmacokinetic studies were carried out on day 1 and day 15. The results showed that rifampicin concentrations were higher when it was administered with indinavir than when it was administered alone. With concomitant indinavir medication, the mean AUC0-24 of rifampicin was increased by 73%. Therefore, we conclude that indinavir has an inhibitory effect on the metabolism of rifampicin.

The clinical course of Hashimoto's thryoiditis in children and adolescents: 6 years longitudinal follow-up.

Forty-six children and adolescents with Hashimoto's thyroiditis were followed up for 5.9 +/- 0.3 years. The mean age at diagnosis was 12.4 +/- 1.7 years (range 9-15.4 yr). The patients were divided into three groups according to thyroid function: group 1 (n = 28) included patients who had normal concentrations of free thyroxine (FT4) and thyrotropin (TSH); group 2 (n = 8) included patients who had normal FT4 and elevated TSH, consistent with compensated hypothyroidism; group 3 (n = 10) included patients who had low FT4 and elevated TSH consistent with overt hypothyroidism. After 5.9 years of follow-up, four out of eight patients with compensated hypothyroidism had normal thyroid function and the other four patients developed overt hypothyroidism. Thyroxine therapy was administered in patients with overt hypothyroidism including the four patients with compensated hypothyroidism who later presented with overt hypothyroidism. All patients in both euthyroid and hypothyroid groups had normal growth and puberty. Final adult height was 0.43 +/- 0.80 SDS which was 1.58 +/- 3.03 cm above mid-parental height. The mean age at menarche (n = 43) was 12.4 +/- 1.1 years, which was not different from normal children. The goiter remained the same size in most of the patients with euthyroidism without thyroxine therapy, but decreased in patients with overt hypothyroidism after thyroxine therapy.

Haplotype analysis at the FRAXA locus in Thai subjects.

The prevalence of fragile X syndrome (FXS) is approximately 7% in Thai boys with developmental delay of unknown cause. To determine if FXS might have a specific haplotype association, we analyzed 125 unrelated control subjects and 25 unrelated FXS patients using 3 microsatellites, DXS548, FRAXAC1 and FRAXE, and two single nucleotide polymorphisms, ATL1 and IVS10. FRAXAC1 and DXS548 are located approximately 7 kb and approximately 150 kb proximal to the CGG-FMR1 whereas ATL1, IVS10 and FRAXE are located approximately 5.6 kb, approximately 24.5 kb and approximately 600 kb distal to the CGG-FMR1. We found 40 haplotypes in the control group and 14 haplotypes in the FXS group. Of 14 haplotypes in the FXS group, 6 haplotypes were not found in the control group suggesting possible new mutations or admixture of immigrant haplotypes. We observed that most diverse haplotypes came from different FRAXE alleles. For this reason, we analyzed haplotypes composed from the remaining markers alone (DXS548-FRAXAC1-ATL1-IVS10). We found 2 major haplotypes (20-18-G-T and 20-19-A-C) with no significant haplotype differences between the control group (67/125 of 20-18-G-T and 25/125 of 20-19-A-C) and FXS group (16/25 of 20-18-G-T and 6/25 of 20-19-A-C). The other haplotypes found were 33/125 in the control group and 3/25 in the FXS group. The two major haplotypes associated FXS in Thai subjects were the two most common haplotypes in the normal Thai subjects. We could not prove, therefore, that there were founder effects at the FRAXA locus in Thailand. We could not, however, exclude it completely. These findings apparently contrast with most other reports on FXS founder effects in various ethnic groups.

The natural clinical course of children with an initial diagnosis of simple goiter: a 5-year longitudinal follow-up.

A total of 154 children initially diagnosed as simple goiter were evaluated annually for 5 years. The mean age at diagnosis was 12.8 +/- 1.8 years. The annual evaluation consisted of clinical assessment for height, weight, pubertal status, goiter size, and laboratory measurements for free thyroxine (FT4), thyrotropin (TSH), anti-thyroglobulin and anti-microsomal antibodies. At initial diagnosis, goiter was grade I in 117 children (76%) and grade II in 37 children (24%). All children had normal FT4, TSH and negative thyroid antibodies. After 5 years of follow-up, there were 6 children who later had positive thyroid antibodies in the 3rd and 4th year and the diagnosis was changed to chronic lymphocytic thyroiditis. In one patient TSH level was elevated in the third year and later increased which is strongly suggestive of compensated hypothyroidism. All children had normal growth as shown by the average final adult height of 2.67 +/- 1.25 cm above the midparental height. In girls the average age at menarche was 12.5 +/- 1.4 years which was not different from normal children. The goiter decreased in size in 36 children (23.4%) and remained the same size in 113 children (73.4%) without any medication. We concluded that 1) children who were initially diagnosed as simple goiter need to be followed annually for at least 5 years, and 2) the minimal annual laboratory evaluation should be TSH and thyroid antibodies to detect the early stage of chronic lymphocytic thyroiditis and compensated hypothyroidism.

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.

Thyroid autoantibodies in Thai type 1 diabetic patients: clinical significance and their relationship with glutamic acid decarboxylase antibodies.

OBJECTIVE: To study the clinical significance of thyroid autoantibodies in Thai patients with type 1 diabetes and their relationship with glutamic acid decarboxylase antibodies (GAD(65)Ab). METHODS: Thyroglobulin antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab) were measured in 50 Thai type 1 diabetic patients. Forty-four patients also had GAD(65)Ab measured. Serum thyrotropin (TSH) was measured in all patients who had no history of thyroid disease regardless of thyroid antibody status. Clinical data including sex, age at onset and duration of diabetes, family history of diabetes, fasting c-peptide levels as well as frequencies of GAD(65)Ab were compared between patients with and without thyroid antibodies. GAD(65)Ab was also measured in 29 non-diabetic patients with hyperthyroid Graves' disease or Hashimoto thyroiditis as a control group. RESULTS: TG-Ab and TPO-Ab were positive in nine (18%) and 15 (30%) patients, respectively. Eight patients (16%) were positive for both antibodies. Two of 16 patients who were positive for TG-Ab or TPO-Ab had a previous history of hyperthyroidism prior to diabetes onset. Of the remainder, two were newly diagnosed with hyperthyroidism and one was found to have clinical hypothyroidism at the time of the study. None of 34 patients without thyroid antibodies had thyroid dysfunction. Eight patients with positive thyroid antibodies but without clinical thyroid dysfunction and 21 patients without thyroid antibodies were followed for up to 3 years, two patients of the first group developed hypothyroidism, whereas none of the latter developed thyroid dysfunction. The frequency of thyroid dysfunction at the time of initial study was significantly higher in patients with positive thyroid antibodies (3/14 vs. 0/34; P=0.021) and these patients who were initially euthyroid tended to have a higher risk of developing thyroid dysfunction (2/8 vs. 0/21; P=0.069). The frequency of thyroid antibodies was significantly increased in females and in those who had positive GAD(65)Ab. GAD(65)Ab was negative in all of the non-diabetic patients with autoimmune thyroid disease. CONCLUSIONS: About one-fourth of Thai patients with type 1 diabetes without thyroid disease had thyroid antibodies. The frequency of thyroid antibodies was increased in female and in GAD(65)Ab positive patients. The presence of thyroid antibodies is associated with a higher frequency of and may predict a higher risk for thyroid dysfunction in Thai type 1 diabetic patients.

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.

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.

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.

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.

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.

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.

The association of congenital hypothyroidism and congenital gastrointestinal anomalies in Down's syndrome infants.

OBJECTIVE: To study the prevalence of congenital hypothyroidism in infants with Down's syndrome and to verify whether there is an association with other congenital defects. METHODS: This is a prospective study of 112 Down patients, less than 1 year of age, who attended Songklanagarind Hospital from January 1991 to December 1996. Free T4 and TSH determinations were performed in all Down infants. Information on karyotype, sex, maternal age and other congenital anomalies was collected. RESULTS: Congenital hypothyroidism was detected in 17 patients (15.2%); 3 overt congenital hypothyroidism; 6 persistent compensated hypothyroidism; and 8 transient compensated hypothyroidism. Nine of the 20 patients (45%) with congenital gastrointestinal anomalies had congenital hypothyroidism, while 8 out of 92 patients (8.7%) without congenital gastrointestinal anomalies had congenital hypothyroidism. The odds ratio was 8.59 (95% confidence interval 2.4-31.6; p = 0.0001). CONCLUSION: Congenital hypothyroidism has a relatively high prevalence rate in Down infants and tends to occur in Down patients with gastrointestinal anomalies.

Effect of omeprazole on the pharmacokinetics of itraconazole.

OBJECTIVE: To investigate the effect of omeprazole on the pharmacokinetics of itraconazole. METHODS: Eleven healthy volunteers received a single dose of oral itraconazole (200 mg) on days 1 and 15 and oral omeprazole (40 mg) once daily from day 2 to day 15. Itraconazole pharmacokinetics were studied on days 1 and 15. RESULTS: Concentrations of itraconazole were higher when it was taken alone than when it was taken with omeprazole. With concomitant omeprazole treatment, the mean AUC0-24 and Cmax of itraconazole were significantly reduced by 64% and 66%, respectively. CONCLUSION: Omeprazole affects itraconazole kinetics, leading to a reduction in bioavailability and Cmax. These two drugs should not be used together.