Demographics of tonsillar hypertrophy among sickle cell disease patients in calabar.

Background: Sickle cell disease (SCD) is the most common genetic disorder, with Africa bearing the highest burden. In this cohort study, sickle cell subjects are immunocompromised and predisposed to recurrent infections and tonsillar hypertrophy, especially in children. Subsequently, tonsillar hypertrophy leads to sleep-disordered breathing (SDB) with resulting hypoxemia, hypercapnia, and acidosis, raising the risk of HbS polymerization and, consequently, vaso-occlusive phenomena and other complications. Aims: This study aimed to compare tonsillar hypertrophy between sickle cell patients and controls. Materials and Methods: A cross-sectional descriptive study was conducted at, University of Calabar Teaching Hospital, Calabar from September 2019 to September 2021. The cohort of the study was an SCD patient confirmed using hemoglobin electrophoresis at the hematology laboratory of University of Calaabr teaching hospital and recruited via the adult and pediatric hematology unit of University of Calabar teaching hospital, and Calabar sickle cell club. The data were analyzed using Microsoft Excel and IBM Statistical Package and Service Solution (SPSS) version 22. Results: Using Brodsky's grading, the prevalence of grade 3 and 4 hypertrophic tonsils in sickle cell subjects was 41.6% but 17.3% in control. The age range of 0-25 years was the most frequently affected with the peak at 0-5 years. The males among the sickle cell subjects were slightly more affected than the females (M: F =1.2:1), while the females were slightly more in the control (M: F =1:1.1). Conclusions: Hypertrophic tonsils affect control and SCD, but the obstructive grades are commoner in genotypes SCD- Sickle cell disease Haemoglobin SS, SC and AA.

Cytogenetic studies of Hynobiidae (Urodela)XVIII. A ZZ/ZW sex-determining mechanism in a hynobiid salamander species, Hynobius tokyoensis Tago.

The karyotype of Hynobius tokyoensis (2n = 56) was analyzed using three kinds of banding methods to determine the morphological differentiation of the sex chromosomes of this species. Salamanders and egg sacs were collected from seven localities around Tokyo, Japan. Of 28 chromosome pairs, microchromosome No. 21 was identified as a ZZ/ZW-type sex chromosome. The Z chromosome was acrocentric, whereas the W chromosome was submetacentric, with a heterochromatic, elongated short arm. Interestingly, the W chromosome is of three distinct types, W(A), W(B), and W(C), based on R-banding and Ag-NOR patterns. W(A) was detected in five populations from southern habitats, whereas W(B) and W(C) were detected in one population each from northern habitats. W(A), W(B), and W(C) were all found to carry Ag-NORs on their heterochromatic short arms. Considering the karyotypes of other species belonging to the same genus, we discuss the evolution of the sex chromosomes of H. tokyoensis.

Mutation analysis of phenylketonuria in Yamagata prefecture, Japan.

BACKGROUND: We have screened 309,914 newborns in Yamagata prefecture, Japan, since 1977 and have detected four patients with phenylketonuria (PKU). We analyzed the phenylalanine hydroxylase (PAH) gene of the four patients to study the genetic background in this area and the genotype-phenotype relationship in these patients. METHODS: Mutations of the PAH gene were screened by denaturing gradient gel electrophoresis analysis and the sequences were determined. RESULTS: Three cases were compound heterozygotes of six different mutations of the PAH gene and the remaining case was a homozygote. Of the six detected mutations, K115fs is novel, whereas the others have been previously detected among Chinese and/or Japanese patients. CONCLUSIONS: The incidence and genetic basis in Yamagata prefecture was similar to that of other parts of Japan. Analysis of the genotype is useful to understand the clinical variation in some families.

Intermittent jaundice in patients with acute leukaemia: a common mutation of the bilirubin uridine-diphosphate glucuronosyltransferase gene among Asians.

The Gly71Arg mutation of the hepatic bilirubin UDP glucuronosyl-transferase (B-UGT) gene associated with Gilbert syndrome prevails among Japanese and its gene frequency is 0.13. Among 20 patients with acute leukaemia, 4 patients showed intermittent unconjugated hyperbilirubinaemia during the course of combined chemotherapy. The Gly71Arg mutation was detected in all 4 patients with hyperbilirubinaemia, but was not found in 16 patients without hyperbilirubinaemia. Two of them were heterozygotes and one was a homozygote for the Gly71Arg mutation, and the other was a compound heterozygote of the Gly71Arg mutation and TA insertion mutation in the TATA box of the B-UGT gene. In addition to the complications leading to hyperbilirubinaemia, including liver damage due to drugs, viral infections or tumour cell infiltrations and alloimmune haemolysis, carrier status for the Gly71Arg mutation should be considered in a patient with leukaemia showing intermittent hyperbilirubinaemia during the course of chemotherapy, especially among Japanese, Koreans and Chinese owing to its prevalence in those populations.

Neonatal hyperbilirubinemia and a common mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese.

Neonatal hyperbilirubinemia, which is prevalent among Asian peoples, has been considered as a physiological phenomenon, and its metabolic basis has not been clearly explained. Gilbert syndrome is a common inherited disease of unconjugated hyperbilirubinemia due to decreased bilirubin uridine diphosphate-glucuronosyltransferase (B-UGT), and its role in neonatal jaundice has recently been considered. We have previously reported that the Gly71Arg mutation of the B-UGT gene associated with Gilbert syndrome is prevalent in Japanese, Korean, and Chinese populations and was more frequently detected in neonates with severe hyperbilirubinemia than in control subjects. We have studied 159 Japanese full-term neonates, evaluating the relationship between the B-UGT genotype and the severity of jaundice, as assessed with a transcutaneous bilirubinometer. The gene frequency of the Gly71Arg mutation in these neonates was 0.19, and neonates carrying the Gly71Arg mutation had significantly increased bilirubin levels on days 2-4, manifested in a gene dose-dependent manner. The frequency of the Gly71Arg mutation was 0.47 in the neonates who required phototherapy (i.e., those with more severe hyperbilirubinemia), significantly higher than 0.16 in the neonates who did not require the therapy. The gene frequency of the TA repeat promoter polymorphism, the (TA)7 mutation, was 0.07, and neonates carrying this mutation did not have an increase in bilirubin. These results suggested that the Gly71Arg mutation contributes to the high incidence of neonatal hyperbilirubinemia in Japanese.

Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese.

We analyzed the bilirubin uridine diphosphate-glucuronosyltransferase (B-UGT) gene in 42 Japanese newborns with hyperbilirubinemia and determined that 21 infants were heterozygous while 3 was homozygous for Gly71Arg. Allele frequency of Gly71Arg was 0.32 in newborns with hyperbilirubinemia, which was significantly higher than 0.13 in healthy Japanese controls. This mutant allele is also prevalent among Korean and Chinese healthy controls with a frequency of 0.23 in both populations. However, this mutation was not detected in 50 healthy German controls. These data suggest that the high frequency of the Gly71Arg mutation of the B-UGT gene is associated with high incidence of neonatal hyperbilirubinemia in Japanese, Korean and Chinese populations.

New form of platyspondylic lethal chondrodysplasia.

We report on a sporadic case of hitherto unknown lethal skeletal dysplasia. The cardinal clinical manifestations consisted of frontal bossing, cloudy corneae, low nasal ridge, and micrognathia, hypoplastic thorax, and rhizomelic micromelia. Laryngoscopy and neck CT disclosed laryngeal stenosis, and brain CT demonstrated hypoplasia of the corpus callosum. Skeletal survey demonstrated hypoplasia of facial bones and short skull base, extremely severe platyspondyly, hypoplastic ilia, and delayed epiphyseal ossification and rhizomelic shortness of tubular bones. The long bones appeared overtubulated with exaggerated metaphyseal flaring. The humeri were particularly short and bowed. Bowing of the radii and ulnae with subluxation of radial heads presented as a Madelung-like deformity. Unlike the long bones, the short tubular bones were not short and normally modeled. The skeletal changes were superficially similar to those in a group of lethal platyspondylic chondrodysplasias, but were inconsistent with any known subtypes of this group or other lethal skeletal dysplasias.

[Human and animal studies on the pharmacokinetics of norfloxacin in renal failure].

The pharmacokinetics of norfloxacin (NFLX) was studied in 5 patients with chronic renal failure and rats with renal obstruction. The drug was orally given to patients on on- and off-dialysis days in a crossover fashion. Serum levels of NFLX showed a similar profile during both on- and off-dialysis days, and the hemodialysis treatment did not affect the elimination of the drug from the serum. The mean serum elimination half-life was 8.8 +/- 1.2 hours (standard error) for on- dialysis day and it was 7.0 +/- 0.8 hours for off-dialysis day. The urinary recovery of NFLX for 24 hours was less than 0.1% of administered doses in these patients. Rats with renal obstruction exhibited higher drug levels in serum for longer periods of time and elevated biliary excretion ratios in comparison to sham-operated rats, and no significant change in the fraction of biliary metabolites was observed. The biliary excretion of NFLX was likely to be enhanced in patients with renal failure.