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.

An infant with double trisomy (48,XXX, + 18)

We report on an infant with double trisomy 48,XXX, + 18. She presented with manifestations of trisomy 18: prominent occiput, microphthalmia, small mouth, micrognathia, malformed ears, congenital heart defect, overlapping fingers, talipes equinovarus, and rockerbottom feet. An extra palmar crease was present only on the right hand. This patient was alive at 12 months. The clinical manifestations are compared with those of 10 previously reported cases.

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.

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.

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 inhibitory effect of amiodarone and desethylamiodarone on dextromethorphan O-demethylation in human and rat liver microsomes.

Amiodarone has been shown in-vitro to inhibit the activity of cytochrome P4502D6 (CYP2D6) in nonhuman primates. However, the influence of its major metabolite, desethylamiodarone, on this isozyme activity has not been studied. To determine the effect of these drugs on dextromethorphan O-demethylation, we carried out studies in 10 human and 10 rat liver microsomal preparations. In human microsomal studies, amiodarone and the metabolite competitively inhibited dextromethorphan metabolism with mean Ki values of 52.70 +/- 5.27 and 34.40 +/- 3.30 microM, respectively. Similar studies in rat microsomes showed a competitive inhibitory effect of amiodarone and its metabolite on dextromethorphan metabolism. These data suggest that amiodarone and desethylamiodarone have an inhibitory effect on CYP2D6 in man and CYP2D1 in rats. However, it cannot be concluded that both of them are substrates of this isozyme activity.

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.

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.

Growth pattern and age at menarche of obese girls in a transitional society.

Childhood obesity is an increasing problem in a transitional society such as Thailand. To study physical growth and puberty in obese children, a cross-sectional survey of growth and age at menarche was carried out in schoolgirls aged between 8 and 16 years old. The 3,120 girls were divided into two groups based on weight-for-height criteria. Girls with weight-for-height between 80 and 120% were classified as normal stature (2,625; 84.1%) and those more than 120% were obese (495; 15.9%). Using probit analysis, age at menarche in obese girls was 0.9 year earlier than normal stature girls (11.5 years vs 12.4 years). At age 12, obese girls were reaching menarche 2.8 times more when compared with the normal stature girls. In terms of growth pattern, obese girls were taller and grew faster during the prepubertal period, and then reached their final height earlier than the normal stature girls (13 years vs 15 years). The final height in obese girls was significantly shorter (153.0 cm and 155.0 cm, p = 0.01). We conclude that: 1) obese girls grow faster, have earlier menarche and then stop growing earlier, and 2) obese girls tend to be shorter as adults, compared with normal stature girls.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.