Intratumoral injection of rhenium-188 microspheres into an animal model of hepatoma.

UNLABELLED: Intratumoral injection of 90Y microspheres is a potential alternative in the treatment of primary liver tumor. However, complicated preparation and lack of a gamma ray for imaging are the disadvantages of 90Y. In this study, we used 188Re, a generator-produced radioisotope with 155-keV gamma ray emission, to label microspheres. After intratumoral injection of 188Re microspheres into rats with hepatoma, biodistributions and survival times were analyzed. METHODS: Twelve male rats with hepatoma were killed at 1, 24 and 48 hr (4 rats at each time point) after intratumoral injection of approximately 7.4 MBq 188Re microspheres. Samples of various organs were obtained and used to calculate the tissue concentrations. In addition, 30 male rats bearing hepatoma were divided into two groups (15 rats in each group) to evaluate survival time. Group 1 received intratumoral injection of 37 MBq 188Re microspheres, whereas Group 2 served as the control group and received an intratumoral injection of 0.1 ml normal saline only. Survival time was calculated from the day of injection to 2 mo after treatment. RESULTS: Radioactivity in the tumor was very high throughout. Biological half-time was 170.8 hr. Radioactivity in the lung was 1.78% injected dose (i.d.)/g at 1 hr but declined rapidly over time. The concentration in the urine was approximately 6.14% i.d./ml after the first hour and rapidly declined thereafter. The concentrations of radioactivity in other organs, such as normal liver, muscle, spleen, bone, testis and whole blood, were quite low throughout the study. Twelve of 15 (80%) of rats survived over 60 days after intratumoral injection of 188Re microspheres, whereas only 4 of 15 (26.7%) survived more than 60 days after injection of normal saline only. The difference between the groups was significant (p < 0.05). CONCLUSION: Rhenium-188 offers cost-effectiveness, on-site availability, short half-life, energetic beta particle, emission of gamma photons for imaging, easy preparation, easy clinical administration and apparent lack of radiation leakage from the treated tumor. Direct intratumoral injection of 188Re microspheres is extremely attractive as a clinical therapeutic alternative in hepatoma patients.

Alagille syndrome with interstitial 20p deletion derived from maternal ins(7;20).

We present a 6-year-old Chinese boy with Alagille syndrome and an interstitial 20p deletion, with a karyotype of 46,XY,der(20)dir ins(7;20)(q11.23;p11.23p12.2 or p12.2p13)mat. He had a peculiar face and suffered from congenital heart disease, growth retardation, severe cholestasis, hepatosplenomegaly, and impaired renal function. The karyotype of his mother showed a balanced translocation, 46,XX,dir ins(7;20)(q11.23; p11.23p12.2 or p12.2p13), and her phenotype was normal. His dead elder brother was highly suspected as another victim of Alagille syndrome. The findings in the present family suggested that if Alagille syndrome is a single gene defect, the putative gene responsible for the syndrome would not be located at the insertion breakpoints but located within the deletion extent.

Viral encephalitis in children: detection with technetium-99m HMPAO brain single-photon emission CT and its value in prediction of outcome.

PURPOSE: To assess the role of regional cerebral blood flow measured by technetium-99m hexamethyl propyleneamine oxime (HMPAO) brain single-photon emission CT (SPECT) in viral encephalitis of children. METHODS: Eighteen children diagnosed as having viral encephalitis (12 Epstein-Barr virus, 4 herpes simplex virus, and 2 Japanese B virus) underwent Tc-99m HMPAO brain SPECT and brain MR and/or CT. RESULTS: During the acute episode, 4 (22%) of the 18 patients had localized abnormality on brain MR and/or CT. Tc-99m HMPAO brain SPECT in the acute phase showed that 17 (94%) of the 18 patients had increased regional cerebral blood flow and 1 (6%) of the 18 children had a normal brain SPECT. Follow-up brain SPECT was performed at least 15 days after the acute episode. In 17 patients with abnormal first brain SPECT, 12 (71%) had normal second brain SPECT and 5 (29%) had decreased regional cerebral blood flow. The group of patients with normal regional cerebral blood flow on the follow-up brain SPECT had a better outcome than the group of patients with decreased regional cerebral blood flow. CONCLUSIONS: (a) The Tc-99m HMPAO brain SPECT was abnormal more often than CT or MR in children with acute viral encephalitis and provided better location. (b) In acute episodes of encephalitis, most patients showed locally increased regional cerebral blood flow. (c) After acute episodes, the regional cerebral blood flow returned to normal in most cases. (d) A normal Tc-99m HMPAO brain SPECT in the subacute phase usually indicates a good clinical outcome (no neurologic defect) 1 year after the acute illness in children with viral encephalitis.

Poor agreement between dipyridamole-stress technetium-99m-tetrofosmin myocardial perfusion single photon emission computed tomography and two-dimensional echocardiography in Kawasaki disease.

To establish a noninvasive diagnostic method for early assessment of cardiac involvement in Kawasaki disease (KD), 28 children with KD were included in this study. Two-dimensional echocardiography (2D-Echo) to detect the aneurysms of coronary arteries (CA), as well as rest and dipyridamole-stress technetium-99m tetrofosmin (Tc-TF) myocardial perfusion single photon emission computed tomography (SPECT) to detect abnormal myocardial perfusion were performed in all of the 28 children with KD and to compare each other. The results showed that (1). 42.9% of cases had no aneurysm and 57.1% had significant aneurysms detected by 2D-Echo; (2). 42.9% of cases had normal perfusion and 57.1% of cases had abnormal myocardial perfusion assessed by Tc-TF myocardial perfusion SPECT; (3). 25.0% of cases showed both normal 2D-Echo and Tc-TF myocardial perfusion SPECT findings and 39.3% of cases showed both abnormal 2D-Echo and Tc-TF myocardial perfusion SPECT findings; and (4). there was poor agreement between 2D-Echo and Tc-TF myocardial perfusion SPECT findings (P>0.05). We concluded that poor agreement exists between aneurysms and abnormal myocardial perfusion detected by 2D-Echo and Tc-TF myocardial perfusion SPECT findings in patients with KD.

Neonatal fungemia caused by Hansenula anomala: a case report.

Hansenula anomala, an ascosporogenous yeast of the class Ascomycetes, is a free-living organism isolated from the environment. It is also a part of the normal or transient flora of the human throat and alimentary tract. It has been recognized as an opportunistic pathogen and its infection is very rare. A premature infant, a victim of right femoral osteomyelitis and right hip arthritis caused by oxacillin-resistant Staphylococcus aureus, was found to have developed H. anomala fungemia just before the initiation of the antimicrobial therapy with teicoplanin. Antifungal agents (fluconazole and amphotericin B) were prescribed for 10 days despite the absence of clinical sign of systemic fungal infection. His general condition remained good, with a subsequent sterile blood culture. The patient was discharged after completing 5 weeks of antimicrobial therapy, and he remained well during follow-up at our outpatient clinics. Here, we also review the risk factors, the clinical presentations, and the therapeutic strategies of H. anomala infection in the literature.

Invasive Streptococcus pneumoniae infections of children in central Taiwan.

We carried out a retrospective study on childhood invasive pneumococcal infections (IPI) diagnosed from the January 1990 through the April 2000 at a medical center in central Taiwan. Their clinical features, outcome of the patients and the resistance patterns of the isolates were analyzed. A total of 95 clinical isolates from 72 patients younger than 14 years of age were included in this study. Of these 72 patients, 51 had bacteremia, 28 meningitis, 14 bacteremic pneumonia, 12 pleural empyema, eight otitis media, four arthritis, three sinusitis, two periorbital abscesses, one deep neck infection, one psoas muscle abscess, one peritonitis, one urinary tract infection, and one cutaneous infection. Ancillary diagnostic tests, including Gram stain smears and latex agglutination tests, were applied and the sensitivities were 86.2% and 54.3%, respectively. The prevalence rate of penicillin nonsusceptible Streptococcus pneumoniae has increased dramatically since 1995 in central Taiwan, with rates of 5.6% and 74.1% before and after 1995, and the overall mortality rate was 20.8% and 53.3% respectively. Ten of 19 children (52.6%) with pneumococcal meningitis who survived had long-term sequelae.

Chronic granulomatous disease: a case report.

Chronic granulomatous disease (CGD) is a rare inherited disorder caused by defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex of phagocytic leukocytes. The leukocytes of the CGD patients cannot produce adequate amount of superoxide and other oxygen metabolites which are toxic to microorganisms. As a result, the phagocytes fail to kill the ingested microorganisms, especially those with catalase activity. Typically, CGD patients suffer from recurrent pyogenic infections starting from the first year of life. We report a young boy who had experienced recurrent perianal abscess, osteomyelitis and bacterial enterocolitis. Flow cytometric analysis revealed defects in the neutrophil respiratory burst pathway and defined the carrier state of his mother and younger sister. He received antimicrobial prophylaxis at our out-patient clinics and remained well at present. We try to make clinical physician keep in mind the diagnosis of CGD by presenting this typical case. In the meantime, we review the recent literature regarding the advances in diagnosis and management of CGD.

Guillain-Barré syndrome in children: a cooperative study in Taiwan.

Seventy-two children with Guillain-Barré syndrome (GBS), diagnosed at 11 major teaching hospitals in Taiwan during the period 1986-1990, were studied retrospectively. There were 44 males and 28 females ranging in age from 7 months to 15 years. Preceding events could be traced in 61 patients (85%), including antecedent infection in 59 patients and previous vaccination in 2. As well as the consistent pictures of progressive weakness and generalized hyporeflexia, there were sensory complaints (26%), cranial nerve lesions (46%), respiratory failure (14%) and autonomic dysfunction (25%). Motor symptoms reached a maximum within 20 days in 88% of the patients, with the plateau lasting less than 2 weeks in 75%, and became stable within 3 months in 76%. Overall outcome showed complete recovery in 73% of the patients within 6 months after onset. Four (5.6%) had recurrence, and there was no mortality. The present study revealed that the annual incidence of GBS in Taiwan can be estimated roughly as 0.66 per 100,000 and that the course of childhood GBS is relatively benign.

Leigh syndrome with progressive ventriculomegaly.

A 6-month-old female infant was diagnosed with Leigh syndrome after an abnormal muscle specimen was obtained and after magnetic resonance imaging demonstrated characteristic cranial lesions. She presented with episodic hyperventilation, myoclonus, ophthalmoplegia, hypotonia, and elevation of lactate in the cerebrospinal fluid and blood. A series of cranial ultrasounds revealed progressive ventricular enlargement before the typical lesions were detected by magnetic resonance imaging. Myelin destruction is believed to play an important role in the early stage of Leigh syndrome. Ultrasonography may provide a convenient way to document changes in brain that provide early suspicion of Leigh syndrome.

Oral glucose lactate stimulation test in mitochondrial disease.

We selected 23 patients with neurologic diseases, including 15 boys and 8 girls from 1 month to 10 years of age, who were divided into mitochondrial and nonmitochondrial disease groups. All patients were required to fast and rest for at least 4-10 hours before the test. Glucose was administered orally using a 50% glucose:water solution at a dose of 1.75 mg/kg. Blood samples then were drawn from a retained heparinized venous line at 0, 30, 60, 120, and 180 min and tested for lactate and glucose levels. Of the mitochondrial disease group, 10 of 11 patients had an upward sloping curve of lactate metabolism; the one who had a flat line response was a patient who suffered from a free-fatty-acid metabolic defect presenting with a recurrent Reye-like syndrome. There was a relatively flat line response in the nonmitochondrial disease group except in a patient with alternating hemiplegia whose symptoms responded well to flunarizine therapy. A significant increase in blood lactate content at 60 min after glucose loading occurred in the mitochondrial disease group, in contrast to that of the nonmitochondrial group. Sensitivity and specificity of a 5 mg/dl increase in blood lactate concentration at 60 min was 72.7% vs. 91.7% Moreover, all 4 patients whose blood lactate increased by 13 mg/dl at 60 min were in the mitochondrial disease group.

New mutations of the HPRT gene in Lesch-Nyhan syndrome.

Lesch-Nyhan syndrome is an X-linked recessive disorder involving the purine metabolism, with resultant hyperuricemia, choreoathetosis, self-mutilation, and profound neurologic dysfunction. A deficiency of the enzyme hypoxanthine guanine phosphoribosyl-transferase is responsible for the disease. The human HPRT gene is located at Xq26-27 and consists of 57 base pairs. At least 2,000 mutations throughout the HPRT gene coding region from exon 1-9 have been reported. Four patients from three Chinese families were diagnosed with Lesch-Nyhan syndrome according to the clinical and laboratory findings. DNA studies revealed the first family (Patients 1 and 2) had a missense mutation in exon 3 of the HPRT encoding region. This novel mutation occurs in the hot spot of the HPRT gene. The second family (Patient 3) was found to have a missense mutation in exon 8 of the HPRT gene. The third family (Patient 4) carried a mutation in the splicing region of intron 4 of the HPRT gene. All three mutations were de novo.

Leigh syndrome associated with mitochondrial DNA 8993 T-->G mutation and ragged-red fibers.

We report a 6-month-old girl with episodic hyperventilation, myoclonus, disturbed consciousness, and lactic acidosis. Brain sonogram revealed progressive ventriculomegaly, and MRI showed symmetric low densities over the putamen bilaterally with diffuse cortical cystic lesions. Ragged-red fibers were noted in the muscle biopsy. Molecular analysis revealed a heteroplasmic T-->G mutation at nucleotide position (np) 8993 of mitochondrial DNA (mtDNA). The proportion of the mutant mtDNA in the muscle of the proband was estimated to be 86%. Her mother and maternal uncle also harbored the same mutant mtDNA (54 and 48% in their leukocytes, respectively). One of her sisters carried 64% mutant mtDNA in her leukocytes, but another sister did not. These results suggest that this mutant mtDNA is transmitted through the maternal lineage in this family in a randomly segregated manner. To our knowledge, this is the first report of a Chinese patient with Leigh syndrome associated with the T-->G substitution at np 8993 of mtDNA.

MRI of Joubert's syndrome.

OBJECTIVE: To report five cases of the rare Joubert's syndrome. SUBJECTS: All five cases were studied by 1.0-Tesla MRI. All the patients showed typical clinical manifestations of Joubert's syndrome including neonatal respiratory abnormalities, developmental delay, ataxia, retinal atrophy and nystagmus. RESULTS: The T1WI of MRI showed characteristic MRI features of Joubert's syndrome including dilatation of the fourth ventricle with some appearing bat-wing shaped, elongation and stretching of the superior cerebellar peduncles, dysphasia of the vermis, widening of the foramen of Magendie and the posterior cistern. One case was associated with encephalomeningocele. CONCLUSIONS: MRI can provide characteristic findings of Joubert's syndrome and confirm the clinical diagnosis.

Comparison of 201Tl SPET and treadmill exercise testing in patients with Kawasaki disease.

About 4% of children with Kawasaki disease ultimately develop ischaemic heart disease. Therefore, the early detection, non-invasive monitoring and long-term follow-up of myocardial ischaemia are essential. We compared the sensitivity and specificity of 201Tl single photon emission tomography (SPET) and treadmill exercise in the detection of myocardial ischaemia in 23 patients (19 boys, 4 girls) with Kawasaki disease. They were divided into two groups according to the results of coronary angiography. Group I consisted of 11 patients with coronary abnormalities; Group II consisted of 12 patients with no coronary abnormalities. The sensitivity, specificity, false-positive and false-negative rates for detecting coronary arterial lesions were 72.7% (8/11), 58.3% (7/12), 38.5% (5/13) and 30% (3/10) for 201Tl SPET, and 45.5% (5/11), 100% (12/12), 0% (0/5) and 33.3% (6/18) for treadmill exercise, respectively. We conclude that 201Tl SPET is more sensitive than treadmill exercise for the detection of coronary arterial abnormalities, but that the specificity of treadmill exercise is better than that of 201Tl scintigraphy. Coronary artery lesions detected by coronary angiography have good concordance of ischaemic areas with perfusion defects detected by 201Tl SPET. When ischaemic findings on 201Tl SPET and/or positive treadmill exercise testing are noted, coronary angiography is strongly indicated to detect possible stenotic lesions in the coronary arteries.

An acute pleuropneumonia in a pig caused by Chromobacterium violaceum.

A 2.5-month-old, 30 kg Duroc pig died 10 days after showing clinical signs of dyspnoea and diarrhoea. Acute necrotizing and fibrinous pleuropneumonia with locally extensive lesions was found. Chromobacterium violaceum was isolated from pneumonic lung tissues and intratracheal inoculation of a pure culture into two SPF pigs reproduced lesions similar to those found in the natural infection.

The effect of breast- and bottle-feeding on oxygen saturation and body temperature in preterm infants.

From July 1997 to June 1998, 25 preterm infants (birth weight < 1800 g) were included in a prospective study to compare the clinical effects of breast- and bottle-feeding. Oxygen saturation, heart rate, respiratory rate, and body temperature were recorded every minute for 20 minutes during feeding periods. Eighty pairs of breast- and bottle-feeding sessions were observed at the chronological age of 9.3 +/- 4.3 (range = 2.1-25.3) weeks. Oxygen saturation and body temperature of the preterm infants were significantly higher when they were directly breastfed. There were 2 episodes of apnea (breath pause more than 20 seconds) and 20 episodes of oxygen desaturation (PaO2 < 90%) during bottle-feeding and none during breastfeeding. We conclude that breastfeeding is a more physiological feeding method for the preterm infant and bottle-feeding may be more stressful.

Tc-99m HMPAO brain SPECT findings in pediatric viral encephalitis.

Two children were diagnosed with viral encephalitis, due to Epstein-Barr virus infection in one case and to herpes simplex virus infection in the other. Tc-99m HMPAO brain SPECT was arranged to detect changes in regional cerebral blood flow (rCBF) secondary to viral encephalitis. During the acute episode, Tc-99m HMPAO brain SPECT showed that the two cases had increased rCBF. After the acute episode, follow-up brain SPECT was arranged 6 months later. The rCBF in one case was restored to normal on the second brain SPECT, and that in the other case was decreased. The child with normal rCBF in the follow-up brain SPECT had better learning ability and intelligence than the other child with decreased rCBF.

Levamisole in steroid-sensitive nephrotic syndrome children with steroid-dependency and/or frequent relapses.

The study is to evaluate the effect of levamisole on steroid-sensitive nephrotic syndrome (SSNS) children with multiple relapses, from October 1996 through December 1998, we prospectively recruited 27 SSNS children. Eight children had minimal change nephrotic syndrome and nine had mesangial nephropathy proven by renal biopsy. The other 10 children had normal renal function and no secondary cause of nephrotic syndrome (NS). Nine were frequent relapsers (FR), (> 4 attack per year), nine were steroid-dependent (SD), and another nine were both FR and SD. The dosage of levamisole given was 2 to 3 mg/kg daily or every other day, depending on the patients' response. All were followed regularly at outpatient department. Follow-up items included a routine urinalysis every month, complete blood count (CBC) every 3 months and BUN/Cr, AST/ALT every 6 months. After 6 to 24 (mean 12.2) months of follow-up, the frequency of relapse (FoR) decreased (5.74 +/- 3.24 vs 1.91 +/- 2.0/year p < 0.05). Seven (26%) had no relapse at all. Nine (33.3%) had less than 1/3 the FoR; four (14.8%) had 1/3 to 1/2 the FoR; and seven (26%) still had more than 1/2 FoR as before levamisole. The oral prednisolone dosage also decreased (0.62 +/- 0.42 vs 0.21 +/- 0.35 mg/kg/day, p < 0.05). The levamisole response was independent of the age of NS onset, the interval between NS onset and initiation of levamisole, previous number of relapse, the FoR, and previous use of cytotoxic drug. There were 7 episodes of leukopenia, which returned to normal after discontinuing levamisole for 1 to 2 weeks in 4 patients. Two (7.5%) had reversible leukopenia for more than 4 weeks. No abnormal BUN/Cr, or ALT/AST levels were noted during follow-up. Levamisole is an effective and safe drug for children who have SSNS with FR and/or SD. Two thirds of patients obtain satisfactory control. The dosage can be 2 to 3 mg/kg daily or every other day. The most common side effect is transient leukopenia.

Breastfeeding knowledge and attitudes of health professionals and students.

Thirty-one physicians, 108 nurses, 105 medical students, and 126 student nurses practicing in the same medical center received a questionnaire to evaluate their knowledge and attitudes about breastfeeding. The mean knowledge score of the 139 staff member was 49.4 +/- 10.8 (The highest possible score was 73); that of the medical students was 31.2 +/- 8.9, and that of the nurse students was 39.5 +/- 7.6. Thirteen percent of the medical students vs. 68.6% of the student nurses reported that they had received breastfeeding education in school. All of the respondents had a positive attitude toward breastfeeding. Occupation and in-service education for breastfeeding could increase the knowledge score. Having been breastfed during infancy could increase both the knowledge score and positive attitude score. We suggest that breastfeeding be integrated into the curricula of both medical and nursing schools. Health professionals should receive in-service education. The mechanism of lactation, management of breast problems and infant problems, contraindications for breastfeeding, the properties of human milk and the benefits of breastfeeding for the infant should all be included.

Individualized developmental care in the newborn intensive care unit.

With recent advances on newborn intensive care, the survival rate of very low birth weight preterm infants has been improved. The consequently new morbidities such as learning disabilities, behavioral problems, lower mean IQ and motor clumsiness have become more frequent. Neonatal individualized developmental care seeks to read the behavior of premature infants, and pace our procedures and caregiving according to individual infant's cues. Studies have shown that with implementation of developmental care, the time spent on ventilator and hospitalization was decreased, and infants started oral feeding earlier. The short and long-term neurobehavioral outcomes were improved. Developmental care focuses not only on changing the environment to provide a calming and soothing environment for the infants and family, but also provides a chance for all the staff members to read the behavior of the infants, think and reflect before doing something to the infants.