In Vitro Chromosomal Radiosensitivity in Fanconi's Anemia

Peripheral blood samples and skin fibroblast cultures from five children withFanconi’s anemia and four normal children were irradiated with 10 and 100rads. Nonirradiated duplicate cultureswere used as controls. Blood cultureswere harvested after 52 and 72 hr ofincubation and fibroblast cultures wereharvested 24 hr after irradiation. Thefrequency of chromosomal breakagecaused by irradiation was calculated bysubtracting figures for nonirradiatedsamples from those for irradiatedsamples. After irradiation, the number ofbreaks/cell/rad in samples from Fanconi’s anemia was approximately four-fold greater in lymphocytes and twofoldgreater in fibroblasts than in the controls.The number of dicentrics and rings percell in cultured lymphocytes after 100rads was significantly greater in the Fanconi’s anemia samples than controls.Therefore, in vitro, chromosomes of cellsfrom children with Fanconi’s anemiawere significantly more radiosensitivethan those of controls (p < 0.01).

Submitted on March 17, 1971 Revised on April 28, 1971 Accepted on April 29, 1971     

Formation, hemodynamics and new management options for gastric varices

Abstract   Gastric varices develop in patients with portal hypertension, including liver cirrhosis, idiopathic portal hypertension as well as left sided-local portal hypertension such as splenic vein thrombosis or splenic AV malformation. The inflow vein is the left gastric vein, posterior vein, or short gastric vein, while the outflow vein is the gastro-renal shunt in most of the patients with gastric varices. The form of the gastric varices is classified into three types of venous dilatation; tortuous type, notched type and tumor type according to the shape and size of the varices. The location is classified into five sites; the posterior site, anterior site, greater curvature site and lesser curvature site of the cardiac area, and the fundic area. The risk of the rupture depends on the mucosal factor of the varices as well as the location and the form. The hemostasis rate has been improved to 94–97% with the usage of the endoscopic occlusive agent such as Histoacryl. It is absolutely necessary to eradicate the gastric varices within a few weeks after rupture of the gastric varices. There are new management options such as laparoscopic Hassab's operation or balloon-occluded retrograde transvenous obliteration of the varices (B-RTO). The 5-year cumulative rate of the non-variceal bleeding is more than 90% after the B-RTO as well as after surgery. Further prospective clinical trials are to be investigated for an evidence-based medicine.     

Classification of gastric lesions associated with portal hypertension

Abstract There are two gastric mucosal lesions which commonly occur in patients with portal hypertension; one is portal hypertensive gastropathy and the other is gastric varices. These lesions occasionally cause fatal haemorrhage. Several classifications for these lesions have been proposed, but none of them have been evaluated prospectively. We consider it better to classify portal hypertensive gastropathy into three stages including non-specific redness, specific mosaic pattern and red spots. Gastric varices may be classified according to form, location and mucosal lesions. Prospective trials are needed to obtain more practical evidence for the accurate classification of these gastric lesions.     

Interleukin-2 receptor positive T and B cells in children with acute severe asthmatic attack

Subpopulations of interleukin-2 receptor (IL-2R)-positive CD4 and CD8 T cells and IL-2R⁺ CD20 B cells in the peripheral blood lymphocytes as well as serum concentrations of soluble IL-2R (sIL2R) were measured in children aged 1–7 years who suffered acute severe asthmatic attack. Subpopulations of CD4⁺ IL-2R⁺ cells, CD8⁺ IL-2R⁺ cells and CD20⁺ IL-2R⁺ cells in the peripheral blood lymphocytes at acute severe asthmatic attack phase were significantly higher than those at non-asthmatic attack phase (P < 0.02, P < 0.03 and P < 0.02, respectively). Subpopulations of CD20⁺ IL-2R⁺ cells in the peripheral blood lymphocytes significantly decreased 5–10 days after acute severe asthmatic attack (at recovery phase, P < 0.02) and were significantly correlated with clinical severity of asthmatic attack (P < 0.05). These results indicated that activation of both T cells and B cells was important in the pathogenesis of acute asthmatic attack in young children.     

Analysis of Met235 to Thr variant of the angiotensinogen gene in relation to the blood pressure and family history of essential hypertension in Japanese children

A recent study reported a significant relationship between a T⁷⁰⁴→C (Met²³⁵→Thr) variant in exon 2 of the angiotensinogen gene in adults and essential hypertension. In the present study, this variant was detected in 131 Japanese children using a polymerase chain reaction. The allele frequency of the variant was 0.76. The genotype frequency of the homozygote for the allele was 0.59, and children who were homozygous had higher systolic blood pressure than those with the other two genotypes. No relationship was found between children's polymorphism and a family history of essential hypertension. These findings suggest that this molecular variant of the angiotensinogen gene may play some role in the regulation of blood pressure in Japanese children.     

Serum level and gene polymorphism of angiotensin I converting enzyme in Japanese children

The aim of the present study was to determine the distribution of the insertion/deletion polymorphism of angiotensin I converting enzyme (ACE) gene in Japanese children. In addition, the relationship between this polymorphism and serum ACE levels in the same population were analyzed. Insertion/deletion polymorphism located in intron 16 of the ACE gene was examined by polymerase chain reaction in Japanese children aged 10–15 years. Allele frequencies were 0.64 for the insertion allele and 0.36 for the deletion allele in 122 subjects. No association was found between genotypes in this polymorphism and the level of systolic or diastolic blood pressure. A significant relationship between this polymorphism and serum ACE activity was observed. These results suggest that interindividual variability of serum ACE level is strongly influenced by the ACE genotype as early as in childhood.     

Congenital hypothyroidism with delayed rise in serum TSH missed on newborn screening

We report on a female patient with congenital hypothyroidism (CH) missed on a newborn screening test. She is now 10 years old with retarded development. The patient was born premature at 34 weeks of gestation with birth-weight of 1515 g, and was judged to be normal in the screening programme of Niigata Prefecture. However, she gradually suffered from poor weight gain and retarded development with stridor at breathing. Serum thyroid stimulating hormone (TSH) levels were rechecked and showed high values with normal T3 and T4 levels. She was referred to our hospital at the age of 13 months. She was diagnosed as having CH (ectopic thyroid) with a delayed rise in blood TSH concentration, probably due to the prematurity of the hypothalamic-pituitary-thyroid axis. l -thyroxine therapy brought a decline in TSH levels with partial improvement of her symptoms. Regardless of the result of newborn screening, infants with elevated serum TSH levels should be carefully examined for possible CH, even when T3, T4 and free T4 values are in the normal range.     

Serum lipoproteins and apolipoprotein E in infants with congenital hypothyroidism

BACKGROUND: Hypothyroid adults have a high risk of atherosclerosis, secondary to increased levels of various cholesterol fractions, particularly low-density lipoprotein cholesterol (LDL-C). We investigated the existence of a correlation between thyroid hormone deficiency and serum lipoproteins and a possible effect of different apolipoprotein E (apoE) phenotypes on lipoprotein levels in 75 infants with hypothyroidism. METHODS: Seventy-three of the 75 infants had congenital hypothyroidism. At the age of one month, prior to the initiation of thyroid hormone substitution therapy, thyroid-stimulating hormone (TSH), thyroid hormones and lipid profile parameters were determined. Subsequently, apoE phenotyping in all patients was performed by isoelectric focusing followed by immunoblotting. RESULTS: Significant negative correlations were identified between triiodothyronine (T3) and LDL-C and total cholesterol (TC) levels and between thyroxine (T4) and TC levels. There were no correlations between TSH and free (F)T4 and lipid profile parameters. Although infants carrying at least one E4 allele had higher LDL-C (as well as TC and triglyceride) levels than those carrying at least one E2 allele, these differences were not statistically significant. No significant differences in thyroid hormones were noted in E4 allele carriers in comparison with other patients. CONCLUSIONS: The observed lack of a significant correlation between thyroid hormones (except T3), apoE phenotypes and lipoprotein levels suggests that, early in infancy, other factors may play a more important role in determining lipoprotein levels.     

Accelerated ventricular rhythm in the newborn

Accelerated ventricular rhythm was observed in two newborn infants. Neither of them had any causative clinical symptoms for the ventricular arrhythmia. The arrhythmia disappeared when the infants were 18 days and 45 days old, respectively. Arrhythmia was noted in the fetal period, especially in case 1.     

Effects of combination therapy with interferon and ofloxacin on chronic type C hepatitis: A pilot study

Interferon is effective in only a limited number of patients with the 1b type of hepatitis C virus (HCV), indicating that a combination therapy with other antiviral drugs may be essential to obtain better results. In the present pilot study, the effects of a combination therapy with interferon (IFN) and an antibacterial drug, ofloxacin, were analysed. Ten patients with chronic type C hepatitis received the combination therapy (combination group). Six million units of natural IFN-α were administered daily for 3 weeks and then three times a week for 21 weeks. The combination therapy was initiated at the beginning of the eighth week of IFN treatment and 600 mg ofloxacin per day was administered for 12 weeks. As a control, changes in HCV-RNA were also analysed in patients who were treated with only IFN for the same period (IFN-alone group). In the combination group, serum transaminase levels and the titres of HCV decreased significantly with ofloxacin administration. Such changes were not observed in the IFN-alone group. The incidence of HCV-negativity at the end of ofloxacin administration of the combination group was significantly higher than in the IFN-alone group. The complete response rate was twice as high in the combination group as in the IFN-alone group. In two patients who did not respond well to the IFN-alone treatment, ofloxacin administration was commenced after the 24th week. Serum transaminase levels were normalized and HCV-RNA became negative in these two patients after the administration of ofloxacin. These results suggest that combination therapy with IFN and ofloxacin may be an effective treatment for chronic type C hepatitis.